Absorption Profile And Bioequivalence Of Two Locally Manufactured Cephalexins

Abstract

The disposition of three locally manufactured oral Cephalexins (two capsules and a suspension) was assessed by estimation of the pharmacokinetic parameters and bioavailability metrics of their constituent (Cephalexin monohydrate), in healthy subjects in comparison with the innovator's brand (Keflex ® ). The study was carried out at the Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum. Ten healthy adult volunteers were included in the study following fulfillment of itsinclusion and exclusion criteria. A randomized three-way and two-way cross over design was performed. Blood samples were collected at specified time after medication with a single dose of cephalexin (2 capsules or 10 ml suspension). Concentrations of cephalexin were measured in plasma by HPLC method using cefotaxim as an internal standard. Non-compartmental pharmacokinetic analysis was performed on the plasma concentrationtime data. The pharmacokinetic parameters(Mean ± SD) of cephalexin following administration of keflex ® capsules, capsules B and capsules C were estimated as Tmax1.10 ± 0.29h, 1.15 ± 0.32h and 1.15 ± 0.32h, Cpmax25.56 ± 6.72µg/ml, 23.95 ± 11.09µg/ml and 13.17 ± 6.97 µg/ml, AUC 45.39 ± 14.94µg.h/ml, 53.48 ± 19.58µg.h/ml and 23.26 ± 12.31 µg.h/ml, MRT 1.99 ± 0.3h, 2.44 ± 0.65h and 1.97 ± 0.3h, Ke 0.709 ± 0.11 h -1 , 0.65 ± 0.14 h -1 and 0.732 ± 0.128 h -1 . t½1.0 ± 0.18 h, 1.11 ±0.22 h and 0.97 ± 0.15 h. CL/F 23.86 ± 6.4 L/h, 21.36 ± 8.56 L/h and 29.59 ± 20.98 L/h. Vd/F 33.87 ± 9.18 L, 35.48 ± 20.22 L and 42.51 ± 35.73 L. The pharmacokinetic parameters (Mean ±SD) of Keflex® suspension and suspension E are in the following order Tmax0.84 ± 0.35 h and 0.90± 0.17 h, Cpmax38.32 ± 4.74 µg/ml and 35.51 ± 11.52 µg/ml, iii AUC∞52.67 ± 10.12µg.h/ml and 54.17 ± 11.52µg/ml, MRT 1.53 ± 0.2h and 1.56 ± 0.19h, Ke 0.87 ± 0.09 h -1 and 0.9 ± 0.08h -1 , T½ 0.81 ± 0.08 h and 0.78 ± 0.07h, CL/F 17.99 ± 3.46 L/h and 21.41 ± 9.88 L/h, Vd/F 20.82 ± 3.7 L and 23.94 ± 10.79 L. Statistical analysis using student'st-test showed that there are no statistically significant differences in all pharmacokinetic parameters between locally manufactured capsules B an C comparedto capsules A (Keflex ® capsules) and suspension E from the local industry compared to reference suspension D (Keflex ® suspension). The relative bioavailability ofcapsules B and capsules C in comparison with the standard brand Keflex ® capsules were 117. . 8 % and 102.48.%, respectively. On the other hand the relative bioavailability of suspension E in comparison with Keflex ® suspension was 102.84%. The study concluded that the absorption profiles and disposition patterns of the locally produced test formulations is highly comparable with that of the standard brands. The tested generics are equally dispositional as the standard brands and gave same plasma level. It is expected that locally manufactured brands will achieve same clinical efficacy as that of the innovator’s brand. Consequently they can be considered bioequivalent with the standard brands and accordingly can be used interchangeably.