Pharmacokinetics and tolerability of voriconazole and a combination oral contraceptive co-administered in healthy female subjects.

What Is Already Known About This Subject: * Voriconazole, a broad-spectrum antifungal drug, is a substrate and inhibitor of CYP2C19 and CYP3A4 isozymes. * Ethinyl oestradiol and norethindrone, components of the combination oral contraceptive drug Ortho-Novum 1/35, also are substrates of cytochrome P450 CYP2C19 and CYP3A4 isozymes. * Because co-administration of voriconazole and Ortho-Novum 1/35 could potentially result in pharmacokinetic interactions that increase systemic exposure of one or both drugs to unsafe levels, clinical studies are needed to define better the two-way pharmacokinetic interaction between these drugs.

Pharmacokinetic interaction between voriconazole and efavirenz at steady state in healthy male subjects.

A randomized, placebo-controlled (with respect to voriconazole), 2-period, multiple-dose intragroup fixed-dose sequence study was conducted in 34 healthy male subjects to evaluate the interactions between voriconazole (triazole antifungal agent) and efavirenz (reverse transcriptase inhibitor). In period 1, subjects received 200 mg twice-daily (bid) voriconazole (n = 17) or placebo (n = 17) for 3 days (400-mg bid loading doses on day 1). In period 2, following a 7-day washout, subjects received 400 mg once-daily (qd) efavirenz alone for 10 days (days 11-20).

Steady-state pharmacokinetic and safety profiles of voriconazole and ritonavir in healthy male subjects.

Since there is a likelihood of coadministration of voriconazole and ritonavir, two studies were conducted to evaluate the potential of drug interaction. Study A was a randomized, placebo-controlled, two-period, parallel-group trial (n = 34). Study B had the same design without the placebo group (n = 17).

Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.

This trial was aimed to estimate the pharmacokinetic interaction between voriconazole and methadone at steady state in male patients on methadone therapy and to characterize the safety and tolerability profile during the coadministration. Twenty-three patients on individualized methadone therapy (30 to 100 mg once daily) were enrolled into this randomized, patient- and investigator-blind, placebo-controlled, parallel-group study. Methadone pharmacokinetic samples were collected from patients receiving methadone alone as the baseline before they were randomized to coadminister either 200 mg voriconazole twice daily (BID) (400-mg BID loading doses on the first day) (n = 16) or matching placebo (n = 7) for the next 5 days.

Safety and pharmacokinetics of coadministered voriconazole and anidulafungin.

There is considerable interest in combining echinocandin and triazole antifungal agents for treatment of invasive fungal infections; however, information is needed regarding the tolerability and potential for pharmacokinetic interactions. Anidulafungin is a semisynthetic echinocandin, and voriconazole is an extended-spectrum triazole. In a random sequence, 17 subjects received anidulafungin with placebo, voriconazole with placebo, and anidulafungin with voriconazole.