title: Bioequivalence study of two oral tablet formulations containing saquinavir mesylate boosted with ritonavir in healthy male subjects.
abstract: Saquinavir (SAQ) mesylate (CAS 149845-06-7) is a potent inhibitor of the HIV-1 protease indicated in combination with other antiretrovirals for the management of HIV-1 infection. The objective of this study was to compare rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 500 mg of SAQ mesylate and the innovator film coated tablet formulation. A randomized, single-center, open-label, two-treatment, two-sequence, three-period, replicated crossover bioequivalence study in 40 healthy male subjects was conducted. All subjects received 100 mg ritonavir (CAS 155213-67-5) twice daily for a run-in period of 3 days before treatment. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 72 h and plasma levels of SAQ were determined by a validated HPLC/UV assay. 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 using the equivalence interval of 80-125%. Point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 94.9 (80.9-111.3), 97.4 (82.4-115.4) and 97.4 (82.5-115.0), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator.
authors.affiliation: F.P. 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: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D018401:Sample Size; D019258:Saquinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D013607:Tablets; D019258:Saquinavir; D019438:Ritonavir