Simulation of metabolism-based herb-drug interaction: towards safe and efficacious use of NIPRD-AM1.

OBJECTIVE: To evaluate the effect of NIPRD-AM1 on CYP3A4 in order to generate clinically significant data for its safe and efficacious use. MATERIALS AND METHODS: NIPRD-AM1 is a phytomedicine developed from aqueous root extracts of Nauclea latifolia Smith (Rubiaceae) for the treatment of uncomplicated malaria. The effect of NIPRD-AM1 on CYP3A4 was measured with and without the addition of NIPRD-AM1, by testing different concentrations of the product at 37 °C in reactive mixtures with ketoconazole (2.5 µM) as the positive control. RESULTS: RESULTS showed a very low IC50 value of 0.01 mg/ml similar to that of ketoconazole (0.016 mg/ml). CONCLUSION: Metabolic processes of NIPRD-AM1 are likely to inhibit CYP3A4, with potential implication on drugs that are CYP3A4 substrates. This is a promising approach for guidance towards the safe and efficacious use of NIPRD-AM1.

Validation of UV Spectrophotometric Method of Analysis of some Marketed Perfloxacin in Nigeria

Background: Acquiring sophisticated LC instruments by most third world laboratories is capital intensive.Literatures on simple spectrophotometric analytical methods for pefloxacin are scarce. Objectives: The present study was undertaken to develop and validate a simple and economic UV spectrophotometric method for estimating pefloxacin mesylate (PFM) in dosage preparations.Methods: Using a JENWAY spectrophotometer at predetermined emax of 277nm with 1 v/v aqueous glacialacetic acid as blank; the method was validated for linearity; accuracy; precision; reproducibility; and specificity asper International Conference on Harmonization (ICH) guidelines and used to determine the content of pefloxacinin seven marketed brands in Nigeria. Results: The method exhibited good linearity over a range of 0.40-12.0 ?g/ml (regression equation: y = 0.0859x+0.0211 ; r=0.999). Mean recovery accuracy (99.183 ) and assay result in the range of 100.5- 110.17 for these lected brands were not significantly different at p=0.05. The coefficient of variation (CV) for both intra andinter-day were below 7 . The method was specific for pefloxacin in the presence of common excipients Conclusion: The method gave good validation results and could be employed for routine analysis of PFM incommercial formulations

The effects of an investigational antimalarial agent, NIPRD-AM1 on the single dose pharmacokinetics of metronidazole in healthy human volunteers.

The effect of concurrent administration of a novel phytomedicine, NIPRD-AM1 used for the treatment of malaria on the pharmacokinetics of metronidazole was investigated in healthy volunteers. The study was a completely randomized one, crossover involving administration of single dose metronidazole tablets (200 mg×2) concomitantly with NIPRD-AM1 capsules (250 mg×2) to 11 healthy volunteers. Blood samples were collected before and at pre-determined time intervals following administration of the drugs. Serum concentrations of the unchanged metronidazole were analyzed using a modified simple and sensitive reversed phase high performance liquid chromatography (HPLC) method. The method showed good precision for metronidazole with coefficient of variation less than 10%. The Pharmacokinetic parameters (AUC, Cmax, and Tmax) were generated using GraphPad Prism software version 2. The derived pharmacokinetic parameters (AUC, Cmax) following the administration of metronidazole alone and co-administration with NIPRD-AM1 were 76.12 µg/ml per hour, 7.94 µg/ml and 73.52 µg/ml per hour, 7.83 µg/ml, respectively. This differences were not statistically significant (P<0.05) and the relative bioavailability was found to be about 96%. The comparable relative bioavailabilty value obtained shows that there is little or no interaction between NIPRD-AM1 and metronidazole. The findings, therefore, showed that metronidazole can be administered with the phytomedicine NIPRD-AM1 without any significant effect on the pharmacokinetic profiles of metronidazole.

Evaluation of phytochemical and antimicrobial properties of leaf extract of Tapinanthus sessilifolius (P. Beauv) van Tiegh.

Leaf extracts of T. sessilifolius growing on five different host plants (Psidium guajava, Citrus lemon, Vernonia amygdalina, Persea americana and Jatropa curcas) were evaluated for antimicrobial activity of the plant. Powdered leaves of T. sessilifolius collected from each host plant was divided into two portions. One portion was used for aqueous infusion and the other portion was successively extracted with hexane, ethylacetate and methanol. Infusion of aqueous extract of powdered leaves did not show antimicrobial effect even at the concentration of 1000 and 2000 microg/ml on test microorganisms (Staph. aureus, E. coli, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans). However in broth culture, methanolic and hexane extract had MIC range of 62.5-500 microg/ml and ethylacetate extract had 250-500 microg/ml. Phytochemical screening of leaf samples of T. sessilifolius collected from different host plants showed positive test for hydrolysable tannins, saponins, flavonoids, terpenes, cardiac glycoside, reducing sugars and proteins. LD50 concentration was found to be > 1.500 mg/kg for samples from P. guajava; 489.89 mg/kg for J. curcas and C. lemon; and 692 mg/kg for V. amydalina in mice.