A Combined‐Formulation Tablet of Lamivudine/Nevirapine/Stavudine: Bioequivalence Compared With Concurrent Administration of Lamivudine, Nevirapine, and Stavudine in Healthy Indian Subjects

Abstract

Generic fixed-dose combinations of antiretrovirals are frequently prescribed for the treatment of human immunodeficiency virus infection. A randomized, 2-way study was conducted in 24 fasting, healthy, Indian male subjects to assess bioequivalence between a single combination tablet containing lamivudine, stavudine, and nevirapine (treatment A) with respect to separate marketed tablets administered simultaneously (treatment B). Each subject received treatments A and B separated by 19 days of a drug-free washout period. Plasma concentrations of antiretrovirals, determined by a validated liquid chromatography/tandem mass spectrometry assay, were used to assess pharmacokinetic parameters such as maximum observed plasma concentration and area under the plasma concentration curve. Pharmacokinetic parameters were comparable for either treatment. As geometric mean ratios (% treatment A/treatment B) of log-transformed parameters of area under the plasma concentration curve and plasma concentration, as well as their resultant 90% confidence intervals, were within 80% to 125% and 75% to 133%, respectively, 2 treatments were considered bioequivalent in the extent and rate of absorption. Both treatments exhibited similar tolerability under fasting conditions.

Generic and low dose antiretroviral therapy in adults and children: implication for scaling up treatment in resource limited settings

“…In a healthy volunteer study, the pharmacokinetic (PK) parameters of the generic FDC of d4T/3TC/NVP was compared to PK parameters of the three branded products, administered simultaneously [5]. Because this was a cross-over study, the patients were used as their own control.…”

High throughput LC–MS/MS method for simultaneous quantification of lamivudine, stavudine and nevirapine in human plasma

“…Both these methods require a total run time of 10 min or more on C-18 reverse phase columns. Recently Narang et al [41] have developed a high throughput LC-MS/MS method to quantify 3TC, d4T and NVP in human plasma with special reference to bioequivalence study. Extraction of plasma was done by SPE involving a reconstitution step to get a LLOQ of 50, 51 and 47 ng/mL for 3TC, d4T and NVP, respectively.…”

Simultaneous determination of lamivudine, stavudine and nevirapine in human plasma by LC–MS/MS and its application to pharmacokinetic study in clinic

“…Since, the logP of 3TC and d4T is −1.11 and −0.81, respectively, LLE is not suitable for these two NRTIs. Recently, Narang et al (2005) and Mistri et al (2007) described an SPE method. However, the sample preparation process was quite time-consuming and not suitable for high throughput sample analysis.…”

“…Aymard et al (2000) and Notari et al (2006) have reported simultaneous determination of these three drugs with other NRTIs, NNRTIs and PIs in human plasma by HPLC-UV with a run time of 40 or 35 min and volume of plasma of 1 or 0.6 mL. LC-MS/MS methods for simultaneous quantifi cation of 3TC, d4T and NVP in human plasma were described by Narang et al (2005), and Mistri et al (2007) used a C 18 reversed-phase column and acid mobile phase with solid-phase extraction (SPE). The lower limit of quantitation (LLOQ) was from 51 to 20 ng/mL.…”