Effects of polysorbate 80 on the pharmacokinetics of a carbamazepine suppository in the rabbit

Abstract

The effect of polysorbate 80 on the rectal absorption of carbamazepine from a fatty suppository was investigated in the rabbit. Each animal received successively (with a wash-out of 1 week between every administration) two oral capsules of 100 mg, a suppository of carbamazepine 200 mg without surfactant, and a suppository of carbamazepine 200 mg including 2% polysorbate 80. After oral administration, the following values were obtained: C max 43 ± 17 μmol/l; T max, 5.1 ± 2.3 h; AUC, 391 ± 204 μmol h l −1. Subsequent to rectal administration of a suppository without polysorbate 80, the corresponding values were: C max, 28 ± 2.9 μmol/l; T max, 2.8 ± 1.3 h; AUC, 203 ± 29 μmol h l −1. The inclusion of polysorbate 80 resulted in a C max of 26 ± 6.2 μmol/l at 1.7 ± 0.5 h. The AUC value amounted to 242 ± 66 μmol h l −1. In the rabbit, rectal administration of carbamazepine from a suppository is more regular than oral absorption from capsules. Polysorbate 80 could enhance the rate and reproducibility of rectal absorption of carbamazepine from a fatty suppository: the serum concentration at 45 min amounted to 20.9 ± 3.8 μmol/l for the suppository containing polysorbate 80 vs 14.6 ± 5.9 μmol/l for that without.