title: Bioequivalence study of two oral tablet formulations containing tenofovir disoproxil fumarate in healthy volunteers.
abstract: Tenofovir disoproxil fumarate (TDF, CAS 147127-20-6) is a nucleotide reverse transcriptase inhibitor which is indicated in combination with other antiretroviral agents for the management of HIV-1 infection. The objective of this study was to compare the rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 300 mg of TDF and the innovator product. A randomized, single-center, open-label, single-dose, two-way crossover bioequivalence study in 40 healthy adult subjects was conducted. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 48 h and plasma levels of tenofovir (TFV) were determined by a validated HPLC assay. Rate and extent of absorption were similar between products. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence between the two formulations using the equivalence interval of 80 and 125%. In healthy subjects, the point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 0.99 (0.92-1.02), 0.99 (0.95-1.03) and 0.93 (0.85-1.02), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator.
authors.affiliation: FP Clinical Pharma, Buenos Aires, Argentina. gyerino@fpclinicalpharma.com.ar
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Yerino
authors.forename: Emilia K
authors.initials: EK
authors.lastname: Halabe
authors.forename: Elvira
authors.initials: E
authors.lastname: Zini
authors.forename: Ethel C
authors.initials: EC
authors.lastname: Feleder
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence; D013607:Tablets; D000068698:Tenofovir; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; D000068698:Tenofovir; D000225:Adenine