Effect of a decoction of Lophira alata (Banks ex P. Gaertn) on the pharmacokinetics of risperidone: Study of a drug-herb interaction

Abstract

Drug interactions may cause a drug to be more or less effective (synergism or antagonism), or cause unexpected effects on the body. Risperidone is a second-generation atypical antipsychotic medication while Lophira alata is a plant used traditionally to treat psychotic disorders. A large number of patients with psychosis have been reported to simultaneously use both orthodox and traditional medicines in Africa. This research was carried out to determine the effect of concomitant administration of risperidone and Lophira alata in healthy human volunteers. The first phase of the research was carried out to establish the baseline pharmacokinetic profile of risperidone 2 mg in 18 male subjects. The second phase was carried out after a 2-week washout period, where the subjects were randomly divided into three equal groups and group A received risperidone 2 mg and decoction of the herb (9.4mg/kg) concurrently, group B received risperidone 2 mg and decoction of the herb (9.4mg/kg) was administered after 1 hour and group C received a decoction of the herb (9.4mg/kg) and risperidone 2 mg was administered after 1 hour. Blood samples were collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after drug administration, and plasma analyses were carried out using a developed RP-HPLC method to determine the plasma concentrations. Subsequently, Kinetica 5.0 software was used to extrapolate pharmacokinetic parameters from the plasma concentrations. Results show that there was a significant (p < 0.05) increase in the rate of absorption (k_a), peak plasma concentration (C_max) and measure of drug exposed to the body (AUC_0-∞) but significant (p < 0.05) decrease in the time to achieve peak plasma concentration (t_max), half-life of absorption (t_1/2a) and extent of drug distribution (Vd) when risperidone and Lophira alata were administered concurrently. Drug-herb interaction was observed to be more significant (p < 0.05), when Lophira alata was administered concurrently with risperidone than when administered one hour before or after Lophira alata. Decoction of Lophira alata interacts with risperidone tablets when administered together, which may be attributed to alteration in the mechanism of risperidone absorption by Lophira alata.