OBJECTIVE: This study aimed to compare the systemic bioavailability of two aciclovir tablets, Rouz-Aciclovir (test) and Zovirax (reference), in 12 healthy volunteers. METHODS: In a crossover design, each subject received a single oral dose of aciclovir 400 mg followed by a 7-day washout period. Plasma concentrations of aciclovir were measured for up to 12 hours using a validated high-performance liquid chromatography method with a lower limit of quantification of 50 microg/L. RESULTS: The mean values of maximum plasma concentration (C(max)), time to C(max) (t(max)), area under the plasma concentration-time curve from time 0 to 12 hours (AUC(12)) and from time 0 to infinity (AUC(infinity)), and plasma half-life following administration of the test product were 999.6 microg/L, 2.08 h, 4911.2 microg/L . h, 5417.7 microg/L . h and 3.08 h, respectively, and for the reference product 775.8 microg/L, 2.58 h, 3862.1 microg/L . h, 4295.4 microg/L . h and 3.14 h, respectively. The test/reference geometric ratio for C(max) (90% CI) was 1.30 (97.1, 174.8). The test/reference geometric ratios for AUC(12) (90% CI) and AUC(infinity) (90% CI) were 1.26 (99.7, 159.1) and 1.24 (98.9, 155.6), respectively. Therefore, the 90% CIs of C(max), AUC(12) and AUC(infinity) were not within the acceptable range of 80 and 125 suggested by the US FDA bioequivalence guideline. CONCLUSION: The results of the present study suggest that the aciclovir test product was not bioequivalent to the reference product. The exact reasons for this remain to be determined. However, we think the difference should be attributed to the difference in the type and amounts of ingredients used in the formulation that probably affect the contact time of aciclovir with the sites of absorption in the gut.
RCT Entities:
OBJECTIVE: This study aimed to compare the systemic bioavailability of two aciclovir tablets, Rouz-Aciclovir (test) and Zovirax (reference), in 12 healthy volunteers. METHODS: In a crossover design, each subject received a single oral dose of aciclovir 400 mg followed by a 7-day washout period. Plasma concentrations of aciclovir were measured for up to 12 hours using a validated high-performance liquid chromatography method with a lower limit of quantification of 50 microg/L. RESULTS: The mean values of maximum plasma concentration (C(max)), time to C(max) (t(max)), area under the plasma concentration-time curve from time 0 to 12 hours (AUC(12)) and from time 0 to infinity (AUC(infinity)), and plasma half-life following administration of the test product were 999.6 microg/L, 2.08 h, 4911.2 microg/L . h, 5417.7 microg/L . h and 3.08 h, respectively, and for the reference product 775.8 microg/L, 2.58 h, 3862.1 microg/L . h, 4295.4 microg/L . h and 3.14 h, respectively. The test/reference geometric ratio for C(max) (90% CI) was 1.30 (97.1, 174.8). The test/reference geometric ratios for AUC(12) (90% CI) and AUC(infinity) (90% CI) were 1.26 (99.7, 159.1) and 1.24 (98.9, 155.6), respectively. Therefore, the 90% CIs of C(max), AUC(12) and AUC(infinity) were not within the acceptable range of 80 and 125 suggested by the US FDA bioequivalence guideline. CONCLUSION: The results of the present study suggest that the aciclovir test product was not bioequivalent to the reference product. The exact reasons for this remain to be determined. However, we think the difference should be attributed to the difference in the type and amounts of ingredients used in the formulation that probably affect the contact time of aciclovir with the sites of absorption in the gut.
Authors: G B Elion; P A Furman; J A Fyfe; P de Miranda; L Beauchamp; H J Schaeffer Journal: Proc Natl Acad Sci U S A Date: 1977-12 Impact factor: 11.205
Authors: Yanhui Lu; Connie Celum; Anna Wald; Jared M Baeten; Frances Cowan; Sinead Delany-Moretlwe; Stewart E Reid; James P Hughes; Ellen Wilcox; Lawrence Corey; Craig W Hendrix Journal: Antimicrob Agents Chemother Date: 2012-02-13 Impact factor: 5.191