Clin Pharmacokinet. 2000 Feb;38(2):111-80. doi: 10.2165/00003088-200038020-00002.
Effects of the antifungal agents on oxidative drug metabolism: clinical relevance.
Clinical pharmacokinetics
K Venkatakrishnan, L L von Moltke, D J Greenblatt
Affiliations
Affiliations
- Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
PMID: 10709776
DOI: 10.2165/00003088-200038020-00002
Abstract
This article reviews the metabolic pharmacokinetic drug-drug interactions with the systemic antifungal agents: the azoles ketoconazole, miconazole, itraconazole and fluconazole, the allylamine terbinafine and the sulfonamide sulfamethoxazole. The majority of these interactions are metabolic and are caused by inhibition of cytochrome P450 (CYP)-mediated hepatic and/or small intestinal metabolism of coadministered drugs. Human liver microsomal studies in vitro, clinical case reports and controlled pharmacokinetic interaction studies in patients or healthy volunteers are reviewed. A brief overview of the CYP system and the contrasting effects of the antifungal agents on the different human drug-metabolising CYP isoforms is followed by discussion of the role of P-glycoprotein in presystemic extraction and the modulation of its function by the antifungal agents. Methods used for in vitro drug interaction studies and in vitro-in vivo scaling are then discussed, with specific emphasis on the azole antifungals. Ketoconazole and itraconazole are potent inhibitors of the major drug-metabolising CYP isoform in humans, CYP3A4. Coadministration of these drugs with CYP3A substrates such as cyclosporin, tacrolimus, alprazolam, triazolam, midazolam, nifedipine, felodipine, simvastatin, lovastatin, vincristine, terfenadine or astemizole can result in clinically significant drug interactions, some of which can be life-threatening. The interactions of ketoconazole with cyclosporin and tacrolimus have been applied for therapeutic purposes to allow a lower dosage and cost of the immunosuppressant and a reduced risk of fungal infections. The potency of fluconazole as a CYP3A4 inhibitor is much lower. Thus, clinical interactions of CYP3A substrates with this azole derivative are of lesser magnitude, and are generally observed only with fluconazole dosages of > or =200 mg/day. Fluconazole, miconazole and sulfamethoxazole are potent inhibitors of CYP2C9. Coadministration of phenytoin, warfarin, sulfamethoxazole and losartan with fluconazole results in clinically significant drug interactions. Fluconazole is a potent inhibitor of CYP2C19 in vitro, although the clinical significance of this has not been investigated. No clinically significant drug interactions have been predicted or documented between the azoles and drugs that are primarily metabolised by CYP1A2, 2D6 or 2E1. Terbinafine is a potent inhibitor of CYP2D6 and may cause clinically significant interactions with coadministered substrates of this isoform, such as nortriptyline, desipramine, perphenazine, metoprolol, encainide and propafenone. On the basis of the existing in vitro and in vivo data, drug interactions of terbinafine with substrates of other CYP isoforms are unlikely.
References
- Nephron. 1992;60(1):125-6 - PubMed
- Drug Metab Dispos. 1992 Jul-Aug;20(4):578-84 - PubMed
- Antimicrob Agents Chemother. 1998 Jul;42(7):1592-6 - PubMed
- Antimicrob Agents Chemother. 1995 Aug;39(8):1835-41 - PubMed
- Eur J Clin Pharmacol. 1989;37(3):279-83 - PubMed
- Clin Pharmacol Ther. 1996 Mar;59(3):332-40 - PubMed
- Clin Pharmacol Ther. 1995 May;57(5):518-24 - PubMed
- Eur J Pharmacol. 1998 Oct 9;358(3):289-94 - PubMed
- Drug Metab Dispos. 1996 Dec;24(12 ):1401-3 - PubMed
- Drug Metab Dispos. 1990 Sep-Oct;18(5):711-9 - PubMed
- J Pharm Pharmacol. 1998 Mar;50(3):265-74 - PubMed
- Mol Pharmacol. 1989 Jul;36(1):89-96 - PubMed
- J Heart Lung Transplant. 1992 Nov-Dec;11(6):1127-32 - PubMed
- Clin Pharmacol Ther. 1975 Sep;18(3):259-72 - PubMed
- Drug Metab Dispos. 1996 Feb;24(2):211-5 - PubMed
- Lancet. 1982 Oct 16;2(8303):882-3 - PubMed
- N Engl J Med. 1991 Feb 28;324(9):580-4 - PubMed
- J Pharmacol Exp Ther. 1996 May;277(2):982-90 - PubMed
- Med J Aust. 1989 Nov 20;151(10):603-4 - PubMed
- Drug Metab Dispos. 1995 Feb;23 (2):207-15 - PubMed
- Eur J Clin Pharmacol. 1994;46(4):309-12 - PubMed
- Ir Med J. 1987 Apr;80(4):123-4 - PubMed
- Psychopharmacology (Berl). 1998 Dec;140(3):293-9 - PubMed
- Adv Drug Deliv Rev. 1997 Sep 15;27(2-3):171-199 - PubMed
- Xenobiotica. 1998 Mar;28(3):293-301 - PubMed
- Drug Metab Dispos. 1996 May;24(5):610-4 - PubMed
- J Clin Pharmacol. 1994 Dec;34(12):1222-7 - PubMed
- Eur J Clin Pharmacol. 1997;52(6):479-85 - PubMed
- Drug Metab Dispos. 1999 Apr;27(4):517-25 - PubMed
- Transplant Proc. 1996 Apr;28(2):907-9 - PubMed
- Pharmacotherapy. 1984 Nov-Dec;4(6):343-73 - PubMed
- N Engl J Med. 1976 Aug 12;295(7):354-7 - PubMed
- J Pharmacol Exp Ther. 1998 Sep;286(3):1253-9 - PubMed
- Psychopharmacology (Berl). 1997 Aug;132(4):402-7 - PubMed
- Br J Clin Pharmacol. 1996 Apr;41(4):291-8 - PubMed
- Br J Clin Pharmacol. 1989 Aug;28(2):166-70 - PubMed
- N Z Med J. 1997 Aug 8;110(1049):300 - PubMed
- Drug Metab Dispos. 1996 Oct;24(10):1047-9 - PubMed
- Pharm Res. 1998 Jul;15(7):1001-6 - PubMed
- Arch Biochem Biophys. 1991 Nov 1;290(2):355-61 - PubMed
- Drug Metab Dispos. 1990 Nov-Dec;18(6):859-65 - PubMed
- Ann Intern Med. 1991 May 1;114(9):755-7 - PubMed
- J Pharmacol Exp Ther. 1999 Jul;290(1):58-65 - PubMed
- Br J Clin Pharmacol. 1988 Jul;26(1):23-9 - PubMed
- BMJ. 1998 Feb 7;316(7129):441 - PubMed
- Chem Pharm Bull (Tokyo). 1992 May;40(5):1247-51 - PubMed
- Eur J Clin Pharmacol. 1998 Apr;54(2):177-83 - PubMed
- Drugs. 1997 Apr;53(4):539-49 - PubMed
- Br J Clin Pharmacol. 1997 Mar;43(3):340-1 - PubMed
- Clin Pharmacol Ther. 1996 Jun;59(6):613-23 - PubMed
- J Heart Lung Transplant. 1991 May-Jun;10(3):351-8 - PubMed
- Drug Metab Dispos. 1999 May;27(5):565-8 - PubMed
- BMJ. 1997 Feb 1;314(7077):349 - PubMed
- N Engl J Med. 1994 Jan 27;330(4):263-72 - PubMed
- Drug Metab Dispos. 1999 Apr;27(4):533-41 - PubMed
- Drug Metab Dispos. 1995 Apr;23 (4):490-6 - PubMed
- Biochem Pharmacol. 1988 Oct 15;37(20):3861-6 - PubMed
- Drug Saf. 1998 Feb;18(2):83-97 - PubMed
- Transplantation. 1993 May;55(5):1000-4 - PubMed
- Clin Pharmacol Ther. 1996 Sep;60(3):326-31 - PubMed
- Lancet. 1989 Jun 3;1(8649):1262 - PubMed
- Clin Pharmacol Ther. 1997 Jul;62(1):41-9 - PubMed
- Ther Drug Monit. 1997 Dec;19(6):609-13 - PubMed
- J Pharmacol Exp Ther. 1998 Apr;285(1):271-6 - PubMed
- Am J Clin Oncol. 1997 Dec;20(6):592-9 - PubMed
- Clin Pharmacokinet. 1999 May;36(5):309-13 - PubMed
- J Heart Transplant. 1987 Mar-Apr;6(2):84-9 - PubMed
- Clin Pharmacol Ther. 1991 Apr;49(4):420-5 - PubMed
- Pharm Res. 1999 Mar;16(3):408-14 - PubMed
- Drug Metab Dispos. 1995 Mar;23(3):406-14 - PubMed
- Lancet. 1982 Dec 11;2(8311):1342 - PubMed
- Neuropsychopharmacology. 1999 May;20(5):480-90 - PubMed
- Clin Pharmacol Ther. 1994 May;55(5):481-5 - PubMed
- Am J Hosp Pharm. 1978 Nov;35(11):1399-401 - PubMed
- Clin Pharmacokinet. 1997 May;32(5):403-25 - PubMed
- Mayo Clin Proc. 1976 Dec;51(12):782-4 - PubMed
- Drug Metab Dispos. 1990 Sep-Oct;18(5):595-606 - PubMed
- Anesth Analg. 1996 Mar;82(3):511-6 - PubMed
- Contraception. 1980 Dec;22(6):643-52 - PubMed
- Clin Infect Dis. 1994 Feb;18(2):266 - PubMed
- Pharmacol Toxicol. 1999 Mar;84(3):143-6 - PubMed
- Clin Pharmacol Ther. 1995 Nov;58(5):556-66 - PubMed
- Arch Dermatol. 1996 Oct;132(10):1254 - PubMed
- Drug Metab Dispos. 1996 Apr;24(4):414-21 - PubMed
- Pharmacology. 1997 Nov;55(5):235-43 - PubMed
- Br Med J (Clin Res Ed). 1982 Oct 9;285(6347):1045-6 - PubMed
- Br J Clin Pharmacol. 1995 Dec;40(6):523-30 - PubMed
- Ther Drug Monit. 1998 Aug;20(4):390-5 - PubMed
- Transplantation. 1996 Feb 27;61(4):537-41 - PubMed
- Br J Clin Pharmacol. 1995 Apr;39(4):421-31 - PubMed
- BMJ. 1990 Oct 6;301(6755):818 - PubMed
- Br J Clin Pharmacol. 1987 Jul;24(1):110-3 - PubMed
- J Pharmacol Exp Ther. 1995 Mar;272(3):984-90 - PubMed
- J Antimicrob Chemother. 1988 May;21(5):633-5 - PubMed
- Acta Med Scand Suppl. 1979;624:106-10 - PubMed
- Transplantation. 1996 Apr 27;61(8):1268-72 - PubMed
- Ann Hematol. 1996 Jan;72(1):17-21 - PubMed
- Int J Clin Pharmacol Ther Toxicol. 1992 Dec;30(12):555-70 - PubMed
- Br J Clin Pharmacol. 1998 Nov;46 Suppl 1:30-4 - PubMed
- J Clin Pharmacol. 1999 Jan;39(1):76-85 - PubMed
- Br J Clin Pharmacol. 1994 Feb;37(2):205-7 - PubMed
- Transplant Proc. 1993 Feb;25(1 Pt 1):591-4 - PubMed
- J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210 - PubMed
- Drug Metab Dispos. 1998 Jun;26(6):572-5 - PubMed
- Am J Ophthalmol. 1998 Jan;125(1):106-8 - PubMed
- Drug Metab Dispos. 1999 Jun;27(6):655-66 - PubMed
- Drug Metab Dispos. 1999 Mar;27(3):395-402 - PubMed
- Clin Pharmacokinet. 1995;29 Suppl 1:33-43; discussion 43-4 - PubMed
- Biochem Pharmacol. 1995 Jul 17;50(2):205-11 - PubMed
- Drug Metab Dispos. 1997 Dec;25(12):1359-69 - PubMed
- Clin Infect Dis. 1993 Mar;16(3):400-3 - PubMed
- Aust N Z J Med. 1991 Dec;21(6):928 - PubMed
- Br J Clin Pharmacol. 1998 Feb;45(2):107-14 - PubMed
- Int J Clin Pharmacol Ther. 1998 Jan;36(1):9-13 - PubMed
- N Engl J Med. 1994 May 5;330(18):1315-6 - PubMed
- Br J Clin Pharmacol. 1992 Jul;34(1):75-8 - PubMed
- Drug Metab Dispos. 1999 Jul;27(7):804-9 - PubMed
- Br J Clin Pharmacol. 1996 Apr;41(4):319-23 - PubMed
- Biochem Pharmacol. 1994 Mar 29;47(7):1157-63 - PubMed
- Rev Infect Dis. 1990 Mar-Apr;12 Suppl 3:S318-26 - PubMed
- Pharmacotherapy. 1990;10(2):146-53 - PubMed
- BMJ. 1993 Jan 16;306(6871):186 - PubMed
- J Infect Dis. 1995 Dec;172(6):1634-6 - PubMed
- Antimicrob Agents Chemother. 1998 Feb;42(2):223-7 - PubMed
- Biochem Biophys Res Commun. 1991 Mar 29;175(3):1112-8 - PubMed
- Transplantation. 1991 Dec;52(6):1086-7 - PubMed
- Clin Pharmacol Ther. 1997 Oct;62(4):417-25 - PubMed
- J Steroid Biochem. 1990 Feb;35(2):281-8 - PubMed
- N Engl J Med. 1996 Jul 25;335(4):290-1 - PubMed
- Drug Metab Dispos. 1996 Apr;24(4):429-35 - PubMed
- Ann Intern Med. 1990 Aug 15;113(4):327-9 - PubMed
- Cell Biol Toxicol. 1997 Jul;13(4-5):365-74 - PubMed
- J Antimicrob Chemother. 1996 Nov;38(5):877-80 - PubMed
- Drug Intell Clin Pharm. 1986 May;20(5):384 - PubMed
- Br J Clin Pharmacol. 1997 Nov;44(5):439-46 - PubMed
- Cancer Res. 1993 Mar 15;53(6):1226-9 - PubMed
- Eur J Clin Pharmacol. 1991;41(6):573-8 - PubMed
- Clin Pharmacol Ther. 1998 Mar;63(3):332-41 - PubMed
- Eur J Clin Pharmacol. 1999 Mar;55(1):57-60 - PubMed
- J Antimicrob Chemother. 1989 Nov;24(5):781-6 - PubMed
- Antimicrob Agents Chemother. 1982 Jan;21(1):151-8 - PubMed
- Br J Clin Pharmacol. 1998 Sep;46(3):271-2 - PubMed
- Br J Dermatol. 1996 Jun;134 Suppl 46:16-7: discussion 38 - PubMed
- Ann Pharmacother. 1995 Oct;29(10):1048-9 - PubMed
- Ann Pharmacother. 1999 Feb;33(2):175-7 - PubMed
- Ann Pharmacother. 1994 Sep;28(9):1111 - PubMed
- J Clin Pharmacol. 1988 Mar;28(3):240-5 - PubMed
- Br J Clin Pharmacol. 1995 Mar;39(3):321-6 - PubMed
- Fundam Clin Pharmacol. 1996;10(3):314-8 - PubMed
- Pharm Res. 1994 Jun;11(6):921-4 - PubMed
- Drug Metab Dispos. 1996 Apr;24(4):487-94 - PubMed
- Antimicrob Agents Chemother. 1997 May;41(5):924-6 - PubMed
- J Pharmacol Exp Ther. 1989 Apr;249(1):134-42 - PubMed
- J Pharmacol Exp Ther. 1988 Oct;247(1):242-7 - PubMed
- J Cardiovasc Pharmacol. 1993 Jan;21(1):77-83 - PubMed
- Clin Infect Dis. 1992 Nov;15(5):886-7 - PubMed
- Pharmacogenetics. 1997 Apr;7(2):103-13 - PubMed
- Biochem Pharmacol. 1994 Apr 29;47(9):1643-53 - PubMed
- Transplantation. 1994 Mar 27;57(6):889-92 - PubMed
- Acta Derm Venereol. 1996 Jul;76(4):280-1 - PubMed
- N Engl J Med. 1980 Jan 3;302(1):33-5 - PubMed
- J Pharmacol Exp Ther. 1995 Nov;275(2):592-7 - PubMed
- Psychopharmacology (Berl). 1998 Oct;139(3):269-73 - PubMed
- Eur J Clin Pharmacol. 1998 Apr;54(2):163-6 - PubMed
- Clin Pharmacol Ther. 1997 Sep;62(3):248-60 - PubMed
- Clin Lab Haematol. 1998 Apr;20(2):123-4 - PubMed
- Cancer Res. 1994 Nov 1;54(21):5543-6 - PubMed
- Eur J Med Res. 1997 Sep 29;2(9):377-83 - PubMed
- J Clin Pharmacol. 1996 Sep;36(9):783-91 - PubMed
- N Z Med J. 1996 Sep 13;109(1029):346 - PubMed
- Ann Hematol. 1995 Dec;71(6):311-2 - PubMed
- Drug Metab Dispos. 1995 Nov;23(11):1253-62 - PubMed
- J Pharmacol Exp Ther. 1982 Oct;223(1):97-104 - PubMed
- Drug Metab Dispos. 1997 Aug;25(8):985-93 - PubMed
- Antimicrob Agents Chemother. 1989 Aug;33(8):1237-41 - PubMed
- Br J Pharmacol. 1993 Sep;110(1):482-90 - PubMed
- Gen Pharmacol. 1996 Mar;27(2):245-9 - PubMed
- J Formos Med Assoc. 1997 Feb;96(2):144-6 - PubMed
- Clin Pharmacokinet. 1995;29 Suppl 1:45-52 - PubMed
- J Pharmacol Exp Ther. 1996 Apr;277(1):423-31 - PubMed
- Clin Pharmacol Ther. 1997 Sep;62(3):348-54 - PubMed
- J Urol. 1994 Feb;151(2):485-91 - PubMed
- Drug Metab Dispos. 1999 Mar;27(3):360-4 - PubMed
- J Med Chem. 1991 Jun;34(6):1838-44 - PubMed
- Arch Intern Med. 1993 Jan 11;153(1):102-4 - PubMed
- Xenobiotica. 1985 Jun;15(6):529-46 - PubMed
- Eur J Clin Pharmacol. 1997;51(5):415-9 - PubMed
- Biochem Pharmacol. 1998 Jan 15;55(2):113-22 - PubMed
- Crit Care Med. 1996 Jul;24(7):1268-71 - PubMed
- Int J Clin Pharmacol Ther. 1998 Aug;36(8):446-9 - PubMed
- Chem Biol Interact. 1999 Apr 1;118(2):171-89 - PubMed
- Int J Clin Pharmacol Ther. 1995 Sep;33(9):518-23 - PubMed
- Transplant Proc. 1998 Feb;30(1):187-8 - PubMed
- Chem Res Toxicol. 1996 Jun;9(4):800-6 - PubMed
- Biopharm Drug Dispos. 1995 Nov;16(8):685-94 - PubMed
- Pharmacol Toxicol. 1990 Jan;66(1):49-52 - PubMed
- Clin Pharmacol Ther. 1986 Jun;39(6):654-9 - PubMed
- Acta Derm Venereol. 1993 Aug;73(4):305-9 - PubMed
- Transplantation. 1991 Feb;51(2):365-70 - PubMed
- Drug Metab Dispos. 1997 Oct;25(10):1191-9 - PubMed
- Ther Drug Monit. 1997 Feb;19(1):56-62 - PubMed
- Drug Metab Dispos. 1996 Sep;24(9):932-9 - PubMed
- Drug Metab Dispos. 1996 Apr;24(4):422-8 - PubMed
- Clin Pharmacol Ther. 1998 Jul;64(1):58-65 - PubMed
- Drug Metab Dispos. 1992 Sep-Oct;20(5):753-61 - PubMed
- Br J Clin Pharmacol. 1999 Feb;47(2):223-5 - PubMed
- Ann Pharmacother. 1995 Oct;29(10):994-6 - PubMed
- Drugs. 1998 Jun;55(6):837-42; discussion 843-4 - PubMed
- FASEB J. 1992 Jan 6;6(2):752-8 - PubMed
- Eur J Clin Pharmacol. 1998 Sep;54(7):561-5 - PubMed
- Mol Carcinog. 1995 Jul;13(3):129-34 - PubMed
- N Engl J Med. 1984 Dec 27;311(26):1681-3 - PubMed
- Pharm Res. 1994 Jul;11(7):961-5 - PubMed
- Pharmacol Toxicol. 1996 Nov;79(5):274-6 - PubMed
- DICP. 1990 Dec;24(12):1177-8 - PubMed
- J Clin Pharmacol. 1997 Nov;37(11):1065-72 - PubMed
- Antimicrob Agents Chemother. 1996 Jan;40(1):230-3 - PubMed
- Clin Pharmacol Ther. 1994 Dec;56(6 Pt 1):601-7 - PubMed
- J Pharmacol Exp Ther. 1999 Apr;289(1):31-7 - PubMed
- Clin Pharmacol Ther. 1987 Oct;42(4):465-70 - PubMed
- Transplant Proc. 1991 Feb;23(1 Pt 2):1041-2 - PubMed
- Transplantation. 1991 May;51(5):1014-8 - PubMed
- Clin Pharmacol Ther. 1995 Jul;58(1):15-9 - PubMed
- Drug Metab Dispos. 1994 Sep-Oct;22(5):811-4 - PubMed
- Eur J Clin Microbiol Infect Dis. 1994 Apr;13(4):330-7 - PubMed
- BMJ. 1990 Sep 29;301(6753):669 - PubMed
- Clin Pharmacol Ther. 1993 Jun;53(6):630-6 - PubMed
- Antimicrob Agents Chemother. 1998 Mar;42(3):695-7 - PubMed
- Biochem Pharmacol. 1992 Apr 15;43(8):1675-82 - PubMed
- Clin Pharmacol Ther. 1998 Sep;64(3):237-47 - PubMed
- Drug Metab Dispos. 1999 Aug;27(8):942-6 - PubMed
- Drug Metab Dispos. 1999 Feb;27(2):173-9 - PubMed
- Clin Pharmacokinet. 1993 Jan;24(1):10-27 - PubMed
- Drug Metab Dispos. 1997 Feb;25(2):256-66 - PubMed
- Clin Pharmacol Ther. 1985 Mar;37(3):290-7 - PubMed
- J Chromatogr. 1986 Apr 25;377:287-94 - PubMed
- Chem Biol Interact. 1997 Oct 24;106(3):161-82 - PubMed
- Clin Pharmacol Ther. 1997 Nov;62(5):510-7 - PubMed
- Lancet. 1995 Aug 12;346(8972):443 - PubMed
- Mol Pharmacol. 1993 Jul;44(1):216-21 - PubMed
- Drug Metab Dispos. 1995 Jan;23(1):154-8 - PubMed
- Ophthalmology. 1997 Apr;104(4):706-11 - PubMed
- Br J Anaesth. 1998 Oct;81(4):598-600 - PubMed
- J Clin Pharmacol. 1997 Mar;37(3):193-200 - PubMed
- Br J Clin Pharmacol. 1997 Mar;43(3):319-22 - PubMed
- Diabete Metab. 1994 Jan-Feb;20(1):49-52 - PubMed
- Clin Pharmacol Ther. 1985 Apr;37(4):407-10 - PubMed
- Lancet. 1987 Dec 5;2(8571):1335-6 - PubMed
- Br J Clin Pharmacol. 1996 Sep;42(3):390-3 - PubMed
- Br J Clin Pharmacol. 1995 Sep;40(3):270-2 - PubMed
- Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4001-5 - PubMed
- J Natl Cancer Inst. 1993 Dec 1;85(23):1921-6 - PubMed
- Clin Pharmacokinet. 1997 May;32(5):357-67 - PubMed
- J Pharmacol Exp Ther. 1999 Apr;289(1):149-55 - PubMed
- Arch Intern Med. 1983 Nov;143(11):2214-5 - PubMed
- J Pharmacol Exp Ther. 1996 Feb;276(2):370-9 - PubMed
- Eur J Clin Pharmacol. 1998 Apr;54(2):167-70 - PubMed
- Eur J Clin Pharmacol. 1998 May;54(3):261-4 - PubMed
- Clin Pharmacol Ther. 1998 Nov;64(5):484-91 - PubMed
- J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300 - PubMed
- Am J Health Syst Pharm. 1998 Feb 1;55(3):233-54 - PubMed
- Clin Pharmacol Ther. 1996 May;59(5):491-502 - PubMed
- Br J Clin Pharmacol. 1996 Jun;41(6):593-604 - PubMed
- Drug Metab Dispos. 1996 Sep;24(9):948-54 - PubMed
- Pharmacotherapy. 1993 Sep-Oct;13(5):508-9 - PubMed
- Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21 - PubMed
- Drug Metab Dispos. 1996 Sep;24(9):955-61 - PubMed
- J Pharmacol Exp Ther. 1998 Oct;287(1):246-52 - PubMed
- Clin Pharmacokinet. 1993 Dec;25(6):450-82 - PubMed
- Am J Hosp Pharm. 1979 Sep;36(9):1155-6 - PubMed
- Clin Infect Dis. 1997 Feb;24(2):270-1 - PubMed
- Clin Pharmacol Ther. 1989 Jul;46(1):78-81 - PubMed
- Biochem Pharmacol. 1994 Jun 1;47(11):1969-79 - PubMed
- Eur J Clin Pharmacol. 1996;50(3):209-15 - PubMed
- Clin Pharmacol Ther. 1975 Oct;18(4):377-90 - PubMed
- Drug Metab Dispos. 1995 Jan;23(1):137-42 - PubMed
- J Pharmacol Exp Ther. 1996 Apr;277(1):321-32 - PubMed
- Eur J Clin Pharmacol. 1996;49(4):309-15 - PubMed
- Ann Pharmacother. 1992 Nov;26(11):1456-7 - PubMed
- Biochem Pharmacol. 1996 Jan 26;51(2):165-72 - PubMed
- Transplant Proc. 1998 Aug;30(5):1685-7 - PubMed
- Br J Clin Pharmacol. 1995 Jul;40(1):83-6 - PubMed
- Antimicrob Agents Chemother. 1995 May;39(5):1050-3 - PubMed
- J Clin Pharmacol. 1993 Oct;33(10):912-7 - PubMed
- J Clin Pharmacol. 1993 Dec;33(12):1201-6 - PubMed
- Pharmacogenetics. 1993 Dec;3(6):291-301 - PubMed
- Drug Metab Dispos. 1995 Jul;23(7):765-75 - PubMed
- J Pharmacol Exp Ther. 1992 Mar;260(3):1052-7 - PubMed
- Cancer Res. 1998 Feb 1;58(3):468-72 - PubMed
- Rev Infect Dis. 1990 Mar-Apr;12 Suppl 3:S327-33 - PubMed
- Br J Dermatol. 1993 Oct;129(4):395-8 - PubMed
- Eur J Clin Pharmacol. 1998 Feb;53(6):445-9 - PubMed
- Am J Med. 1993 Oct;95(4):445-6 - PubMed
- Drug Metab Dispos. 1994 Nov-Dec;22(6):909-15 - PubMed
- J Pharmacol Exp Ther. 1994 Jul;270(1):414-23 - PubMed
- J Heart Lung Transplant. 1996 Nov;15(11):1165 - PubMed
- J Clin Psychopharmacol. 1996 Apr;16(2):104-12 - PubMed
- Br J Clin Pharmacol. 1999 Mar;47(3):291-8 - PubMed
- Br J Clin Pharmacol. 1995 Dec;40(6):531-8 - PubMed
- Lancet. 1982 Nov 27;2(8309):1217 - PubMed
- J Pharmacol Exp Ther. 1995 Dec;275(3):1131-5 - PubMed
- Cancer Res. 1994 Jan 15;54(2):386-92 - PubMed
- Drug Metab Dispos. 1999 Jul;27(7):770-5 - PubMed
- J Pharmacol Exp Ther. 1996 Jun;277(3):1659-64 - PubMed
- J Pharmacol Exp Ther. 1996 Mar;276(3):912-7 - PubMed
- Drug Saf. 1993 Oct;9(4):309-11 - PubMed
- Br J Clin Pharmacol. 1999 Aug;48(2):180-9 - PubMed
- Lancet. 1995 Jan 21;345(8943):191 - PubMed
- J Pharmacol Exp Ther. 1994 Mar;268(3):1278-83 - PubMed
- Am J Obstet Gynecol. 1998 Feb;178(2):300-4 - PubMed
- BMJ. 1999 Apr 17;318(7190):1031-5 - PubMed
- Urology. 1980 Dec;16(6):601-3 - PubMed
- Psychopharmacology (Berl). 1996 Dec;128(4):398-407 - PubMed
- Antimicrob Agents Chemother. 1998 Jul;42(7):1738-44 - PubMed
- Am J Nephrol. 1995;15(6):493-9 - PubMed
- J Clin Pharmacol. 1998 May;38(5):424-8 - PubMed
- J Natl Med Assoc. 1998 Oct;90(10):622-4 - PubMed
- Eur J Clin Pharmacol. 1996;50(1-2):129-31 - PubMed
- Eur J Clin Pharmacol. 1998 Mar;54(1):53-8 - PubMed
- J Clin Invest. 1991 Apr;87(4):1467-9 - PubMed
- Arch Biochem Biophys. 1997 May 1;341(1):47-61 - PubMed
- J Antimicrob Chemother. 1983 Aug;12(2):185-8 - PubMed
- Br Med J (Clin Res Ed). 1983 Dec 10;287(6407):1760 - PubMed
- Eur J Clin Pharmacol. 1993;45(2):191-3 - PubMed
- Dermatologica. 1989;178(1):29-32 - PubMed
- Ther Drug Monit. 1998 Apr;20(2):134-8 - PubMed
- Chemotherapy. 1993;39(1):6-12 - PubMed
- Pharm Res. 1998 Mar;15(3):423-8 - PubMed
- Clin Pharm. 1989 Mar;8(3):222-5 - PubMed
- Br J Clin Pharmacol. 1979;8(1):23S-29S - PubMed
- Anesth Analg. 1996 Jan;82(1):167-72 - PubMed
- Xenobiotica. 1997 Sep;27(9):913-22 - PubMed
- Res Commun Chem Pathol Pharmacol. 1993 Nov;82(2):209-16 - PubMed
- Drug Metab Dispos. 1993 Nov-Dec;21(6):978-85 - PubMed
- Postgrad Med J. 1977 Jul;53(621):388-90 - PubMed
- J Clin Pharmacol. 1999 Jun;39(6):567-77 - PubMed
- Ann Pharmacother. 1993 Apr;27(4):427-30 - PubMed
- Drug Metab Dispos. 1995 Dec;23(12):1315-24 - PubMed
- Xenobiotica. 1995 Mar;25(3):261-70 - PubMed
- Clin Pharm. 1983 Sep-Oct;2(5):441-4 - PubMed
- Antimicrob Agents Chemother. 1990 Mar;34(3):402-8 - PubMed
- Br J Clin Pharmacol. 1999 Jul;48(1):89-97 - PubMed
- Drug Metab Dispos. 1998 Aug;26(8):775-8 - PubMed
- Drug Metab Dispos. 1999 May;27(5):596-9 - PubMed
- Dermatology. 1998;196(2):266-7 - PubMed
- Arch Dermatol. 1996 Mar;132(3):350-2 - PubMed
- Ann Intern Med. 1988 Nov 15;109(10):844-5 - PubMed
- Br J Clin Pharmacol. 1996 Sep;42(3):347-53 - PubMed
- Clin Pharmacol Ther. 1989 Nov;46(5):521-7 - PubMed
- Clin Pharmacol Ther. 1998 Jun;63(6):655-62 - PubMed
- Drug Metab Dispos. 1994 Nov-Dec;22(6):849-57 - PubMed
- Cancer Chemother Pharmacol. 1995;36(2):107-14 - PubMed
- Clin Pharmacol Ther. 1992 Jun;51(6):656-67 - PubMed
- Cancer Res. 1993 Dec 1;53(23):5629-37 - PubMed
- Lancet. 1989 Nov 18;2(8673):1198-201 - PubMed
- N Engl J Med. 1994 May 5;330(18):1316-7 - PubMed
- J Pharmacol Exp Ther. 1998 Sep;286(3):1439-45 - PubMed
- Aust N Z J Med. 1989 Jun;19(3):292-3 - PubMed
- N Z Med J. 1993 Oct 13;106(965):436 - PubMed
- Br J Anaesth. 1994 Nov;73(5):658-61 - PubMed
- Ann Intern Med. 1996 Mar 15;124(6):573-6 - PubMed
- Br J Clin Pharmacol. 1996 Oct;42(4):465-70 - PubMed
- JAMA. 1990 Dec 5;264(21):2788-90 - PubMed
- Br J Clin Pharmacol. 1996 Mar;41(3):187-90 - PubMed
- J Am Acad Dermatol. 1990 Jan;22(1):124-5 - PubMed
- Biochemistry. 1998 Mar 17;37(11):3594-601 - PubMed
- Drug Metab Dispos. 1997 Sep;25(9):1104-6 - PubMed
- J Clin Pharmacol. 1993 Jul;33(7):650-6 - PubMed
- J Pharmacol Exp Ther. 1996 May;277(2):991-8 - PubMed
- Clin Pharmacol Ther. 1992 Mar;51(3):278-87 - PubMed
- Mol Pharmacol. 1986 Sep;30(3):287-95 - PubMed
- Biol Psychiatry. 1999 Sep 15;46(6):839-49 - PubMed
- Lancet. 1992 Jan 25;339(8787):255-6 - PubMed
- Clin Infect Dis. 1994 Feb;18(2):259-60 - PubMed
- J Pharmacol Exp Ther. 1987 Jan;240(1):216-22 - PubMed
- Clin Pharmacol Ther. 1975 Sep;18(3):249-58 - PubMed
- Br J Clin Pharmacol. 1991 Nov;32(5):624-6 - PubMed
- Clin Pharmacol Ther. 1996 Jul;60(1):54-61 - PubMed
- Ther Drug Monit. 1997 Oct;19(5):535-8 - PubMed
- Transplantation. 1993 Dec;56(6):1554-5 - PubMed
- Drug Metab Dispos. 1999 Feb;27(2):180-7 - PubMed
- Drug Metab Dispos. 1993 May-Jun;21(3):403-9 - PubMed
- Lancet. 1987 Aug 1;2(8553):282 - PubMed
- Cancer Res. 1993 Nov 1;53(21):5121-6 - PubMed
- Clin Pharmacol Ther. 1998 Oct;64(4):363-8 - PubMed
- J Pharmacol Exp Ther. 1996 Dec;279(3):1327-34 - PubMed
- Ann Intern Med. 1979 Jul;91(1):34-6 - PubMed
- Anesth Analg. 1998 Jul;87(1):190-4 - PubMed
- Pharmacotherapy. 1997 Jul-Aug;17(4):767-73 - PubMed
- Clin Pharmacokinet. 1997 Mar;32(3):210-58 - PubMed
- Lancet. 1991 Dec 14;338(8781):1488-90 - PubMed
- Ann Intern Med. 1992 Mar 15;116(6):525 - PubMed
- Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7 - PubMed
- Pharmacotherapy. 1997 Jul-Aug;17(4):791-5 - PubMed
- BMJ. 1995 Oct 7;311(7010):919-22 - PubMed
- Br J Clin Pharmacol. 1989 Aug;28(2):161-5 - PubMed
- J Pharmacol Exp Ther. 1997 Oct;283(1):46-58 - PubMed
- Lancet. 1989 Jul 8;2(8654):104-5 - PubMed
- Clin Pharmacokinet. 1988 Jan;14(1):13-34 - PubMed
- Clin Pharmacol Ther. 1999 May;65(5):465-72 - PubMed
- Br J Clin Pharmacol. 1997 Mar;43(3):315-8 - PubMed
- Clin Pharmacol Ther. 1996 Mar;59(3):275-83 - PubMed
- J Invest Dermatol. 1994 May;102(5):740-3 - PubMed
- Eur J Clin Pharmacol. 1989;37(3):231-3 - PubMed
- Naunyn Schmiedebergs Arch Pharmacol. 1999 Feb;359(2):147-51 - PubMed
- Pharmacogenetics. 1997 Feb;7(1):1-10 - PubMed
- Transplantation. 1994 May 27;57(10):1521-3 - PubMed
- J Intern Med. 1995 Nov;238(5):469-72 - PubMed
- BMJ. 1998 Feb 7;316(7129):440 - PubMed
- Drug Metab Dispos. 1996 Mar;24(3):307-14 - PubMed
- Eur J Clin Pharmacol. 1999 Jan;54(11):851-5 - PubMed
- Br J Clin Pharmacol. 1999 Jun;47(6):707-8 - PubMed
- Clin Pharmacol Ther. 1989 Apr;45(4):366-72 - PubMed
- Drug Metab Dispos. 1998 Feb;26(2):188-91 - PubMed
- Drug Intell Clin Pharm. 1987 Jun;21(6):514-7 - PubMed
- Drug Metab Dispos. 1997 Aug;25(8):970-7 - PubMed
- Mol Pharmacol. 1988 May;33(5):500-8 - PubMed
- Pharm Res. 1993 Mar;10(3):418-22 - PubMed
- N Engl J Med. 1995 Sep 7;333(10):664-5 - PubMed
- Clin Pharmacol Ther. 1997 Oct;62(4):384-91 - PubMed
- Br J Clin Pharmacol. 1997 Dec;44(6):557-64 - PubMed
- Chem Res Toxicol. 1992 Jan-Feb;5(1):54-9 - PubMed
- Adv Drug Deliv Rev. 1997 Sep 15;27(2-3):161-170 - PubMed
- J Fam Pract. 1994 Dec;39(6):589-91 - PubMed
- J Clin Invest. 1995 Oct;96(4):1698-705 - PubMed
- Clin Pharmacol Ther. 1989 Jan;45(1):28-33 - PubMed
- Clin Pharmacol Ther. 1997 May;61(5):554-62 - PubMed
- Br J Clin Pharmacol. 1999 Apr;47(4):403-12 - PubMed
- Drug Metab Dispos. 1999 Mar;27(3):417-21 - PubMed
- Clin Pharmacol Ther. 1993 Sep;54(3):257-68 - PubMed
- Clin Pharmacol Ther. 1998 Dec;64(6):661-71 - PubMed
- N Engl J Med. 1995 Sep 7;333(10):628-33 - PubMed
- Br J Clin Pharmacol. 1996 Feb;41(2):149-56 - PubMed
- Pharmacol Ther. 1997;73(1):67-74 - PubMed
- J Pharmacol Exp Ther. 1997 Feb;280(2):927-33 - PubMed
- Eur J Clin Pharmacol. 1993;44(4):349-55 - PubMed
- Clin Pharmacol Ther. 1995 Dec;58(6):617-24 - PubMed
- Antimicrob Agents Chemother. 1997 Sep;41(9):1892-7 - PubMed
- Arch Med Res. 1993 Winter;24(4):387-93 - PubMed
- Lancet. 1987 Mar 21;1(8534):695-6 - PubMed
- Ann Intern Med. 1996 Dec 1;125(11):939-40 - PubMed
- Eur J Clin Pharmacol. 1996;51(3-4):331-4 - PubMed
- Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):417-24 - PubMed
- Eur J Clin Microbiol Infect Dis. 1994 Dec;13(12):1086-7 - PubMed
- J Clin Invest. 1998 Jan 15;101(2):289-94 - PubMed
- Drug Metab Dispos. 1997 Dec;25(12):1379-82 - PubMed
- Lancet. 1982 Dec 11;2(8311):1342-3 - PubMed
- Clin Pharmacol Ther. 1985 Oct;38(4):409-13 - PubMed
- Biochem Pharmacol. 1999 Jun 1;57(11):1227-32 - PubMed
- Antimicrob Agents Chemother. 1995 Dec;39(12):2738-41 - PubMed
- Xenobiotica. 1996 Jul;26(7):681-93 - PubMed
- Clin Infect Dis. 1992 Jan;14(1):165-74 - PubMed
- Pharmacol Toxicol. 1999 Feb;84(2):94-7 - PubMed
- Ann Pharmacother. 1997 Apr;31(4):438-40 - PubMed
- J Pharm Sci. 1998 Jul;87(7):845-53 - PubMed
- J Clin Pharmacol. 1998 Feb;38(2):112-21 - PubMed
- Clin Infect Dis. 1999 Feb;28(2):331-40 - PubMed
- Int J Clin Pharmacol Ther Toxicol. 1986 May;24(5):225-6 - PubMed
- Clin Pharmacol Ther. 1997 Apr;61(4):410-5 - PubMed
- Transplant Proc. 1997 Sep;29(6):2657-9 - PubMed
- J Infect Dis. 1994 May;169(5):1103-7 - PubMed
- Br J Clin Pharmacol. 1998 Jul;46(1):49-53 - PubMed
- J Pharm Sci. 1998 Jul;87(7):803-7 - PubMed
- Ther Hung. 1986;34(3):167-70 - PubMed
- BMJ. 1989 May 13;298(6683):1315 - PubMed
- Drug Metab Dispos. 1998 Jun;26(6):552-61 - PubMed
- Clin Pharmacokinet. 1994 Jul;27(1):1-5 - PubMed
- Clin Pharmacol Ther. 1988 Jun;43(6):630-5 - PubMed
- Mol Pharmacol. 1996 Feb;49(2):311-8 - PubMed
- JAMA. 1993 Mar 24-31;269(12):1513-8 - PubMed
- J Clin Pharmacol. 1991 Apr;31(4):358-61 - PubMed
- Biochem Pharmacol. 1995 Sep 28;50(7):923-8 - PubMed
- Drug Saf. 1995 Mar;12(3):168-82 - PubMed
- Biochem Biophys Res Commun. 1990 Oct 30;172(2):737-44 - PubMed
- Am J Med Sci. 1993 Mar;305(3):164-5 - PubMed
- Ann Intern Med. 1989 May 15;110(10):844 - PubMed
- Transplantation. 1989 Nov;48(5):887-90 - PubMed
- J Pharmacol Exp Ther. 1996 Apr;277(1):105-12 - PubMed
- Drug Metab Dispos. 1995 Jun;23(6):631-6 - PubMed
- Clin Pharmacokinet. 1996 Jan;30(1):52-76 - PubMed
- Cell. 1994 May 20;77(4):491-502 - PubMed
- Lancet. 1985 Jul 27;2(8448):209-10 - PubMed
- Br J Clin Pharmacol. 1994 Jul;38(1):23-31 - PubMed
- Arch Biochem Biophys. 1998 May 1;353(1):16-28 - PubMed
- Ther Drug Monit. 1997 Aug;19(4):436-45 - PubMed
- Biochem Pharmacol. 1997 Apr 25;53(8):1187-95 - PubMed
- Gastroenterology. 1985 Dec;89(6):1235-41 - PubMed
- Pharmacotherapy. 1999 Mar;19(3):281-98 - PubMed
- Lancet. 1975 Dec 6;2(7945):1155-6 - PubMed
- Ann Pharmacother. 1998 Sep;32(9):915-28 - PubMed
- J Am Acad Dermatol. 1995 Jul;33(1):134-5 - PubMed
- Clin Pharmacol Ther. 1991 May;49(5):558-70 - PubMed
- Anticancer Res. 1996 Jul-Aug;16(4A):2083-8 - PubMed
- J Clin Oncol. 1995 Jun;13(6):1501-8 - PubMed
- Clin Pharmacol Ther. 1995 Oct;58(4):412-7 - PubMed
- Br Med J (Clin Res Ed). 1984 Apr 14;288(6424):1125-6 - PubMed
- Psychopharmacology (Berl). 1999 Jul;145(1):113-22 - PubMed
- Transplant Proc. 1994 Oct;26(5):2822 - PubMed
- Ann Pharmacother. 1994 Feb;28(2):191-5 - PubMed
- N Engl J Med. 1990 Jun 21;322(25):1764-8 - PubMed
- Br Med J (Clin Res Ed). 1984 Jan 21;288(6412):188-9 - PubMed
- Methods Enzymol. 1996;272:139-45 - PubMed
- West J Med. 1996 Nov;165(5):322 - PubMed
- Ther Drug Monit. 1996 Apr;18(2):124-7 - PubMed
- DICP. 1989 Nov;23(11):858-61 - PubMed
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