Pharmacokinetic interaction between cefaclor and bromhexine in healthy Chinese volunteers.

Objective: To determine the pharmacokinetic interaction between cefaclor and bromhexine in healthy Chinese volunteers.

Methods: Twelve subjects received a cefaclor (CEF) treatment, a bromhexine (BHX) treatment, and a co-treatment of CEF and BHX with a 3 x 3 Latin square design. The wash-out time between periods was 14 days. The plasma and urine drug concentrations of CEF and BHX were detected by HPLC-UV and LC/MS, respectively.

Results: All the 12 volunteers completed the study. There were no significant differences in AUC 0-t and Cmax of CEF in logarithm between the single administration group of CEF and the co-administration group of CEF with BHX. Two one sided t-test showed that CEF was bioequivalent in the 2 groups. There were no significant differences in tmax, MRT, t1/2, and Clr between the 2 groups. Vd/F was significantly lower in the single CEF group than in the co-administration group of CEF and BHX. There were no significant differences of AUC 0-t and Cmax of BHX in logarithm between the single administration group of BHX and the co-administration group of BHX with CEF. Two one sided t-test showed that BHX was bioequivalent in the 2 groups. There were no significant differences in tmax, MRT, t1/2, Vd/F, and Clr between the 2 groups.

Conclusion: There is no significant pharmacokinetic parameter change in the drug absorption, metabolism, and excretion, but Vd/F of CEF significant increases in the co-administration of CEF with BHX. The co-administration of CEF and BHX has no adverse drug interaction. The increase of Vd/F may be a favorable drug interaction, which may be the mechanism of the synergistic effect of the 2 drugs.