Pharmacokinetic study of the interaction between rifampin and delavirdine mesylate*

Abstract

The findings of this study indicate that rifampin induces the metabolism of delavirdine. Therefore therapy with rifampin is contraindicated in patients receiving delavirdine mesylate.

Simulation of Clinical Drug-Drug Interactions from Hepatocyte CYP3A4 Induction Data and Its Potential Utility in Trial Designs

“…After dosing of 600 mg q.d. of RIF for 8 to 10 days in human subjects, the average plasma unbound concentration reached 0.5 to 1.5 M (Borin et al, 1997;Swaisland et al, 2005). This concentration is much higher than its in vitro unbound EC 50 for induction of 0.1 to 0.2 M, suggesting that at doses of 600 mg and higher CYP3A4 induction is saturated by RIF in vivo.…”

Pharmacokinetic Study of Tenofovir Disoproxil Fumarate Combined with Rifampin in Healthy Volunteers

“…The rifampin dose used (600 mg QD) is an accepted regimen for the treatment of tuberculosis in patients weighing more than 50 kg (7). A previous study (2) has shown that steady-state conditions for rifampin are generally achieved after the sixth daily dose of rifampin at 600 mg. To ensure the achievement of steady-state pharmacokinetics, subjects were given tenofovir DF combined with rifampin for 10 days before pharmacokinetic assessment.…”

“…For determination of the tenofovir and rifampin concentrations in blood plasma, samples of 5 ml of blood, recovered to obtain at least 2 ml of plasma, were collected in heparinized hard plastic tubes at the following times: just before drug intake (predosing); on day 10 and day 20; and at 1,2,3,4,6,8,10,12,16,20, and 24 h after drug intake. The blood samples were centrifuged at 2,500 ϫ g for 10 min at 4°C.…”

Clinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy

“…(DHSS, 2011) Rifampicin and NNRTI. (Finch et al, 2002;de Jong et al, 2004;Ribera et al, 2001;Ramachandran et al, 2006;Weiner et al, 2005) In general, the use of rifampicin together with delavirdine is considered contraindicated (Borin et al, 1997) (level 1: very high risk).…”

“…This combination is considered absolutely contraindicated McCance-Katz et al, 2006;Matteelli et al, 2007a;Ramachandran et al, 2006;Ribera et al, 2001) Delavirdine (Borin et al, 1997;DeJong et al 2004;McCance-Katz et al, 2006;Spradling et al, 2002) Nevirapine (Benator et al, 2007;Blumberg et al, 2003;Borin et al, 1997;Burger et al, 2006;Hamzeh et al, 2003;Kraft et al, 2004;La Porte et al, 2004;Polk et al, 2001;Ramachandran et al, 2006;Ribera et al, 2001Ribera et al, , 2007Rolla et al, 2006) 2: high risk 3: medium risk…”