Purification and partial characterization of laccase from Lachnocladium sp.

Laccase, a multicopper oxidase that catalyzes the oxidation of various aromatics, particularly phenolic substrates, e.g. hydroquinones guaiacol, 2,6-dimethoxyphenol or phenylene diamine, was purified and partially characterised from culture filtrates of a white rot fungus, Lachnocladium sp. This enzyme was purified by anion exchange and gel filtration chromatography. Laccase activity was determined using ABTS (2, 2’-azinobis-(3-ethylbenzthiazoline)-6-sulphonic acid) substrate. The culture filtrate had maximum laccase activity of 1.62 U/ml after 14 days of incubation. The purified laccase had an optimum temperature of 50oC and its optimum pH was 6 for ABTS. The activity of this enzyme was enhanced by Fe2+, Cu2+, Zn2+ and Ca2+, and was inhibited by EDTA and sodium iodide. Laccase from Lachnocladium sp. had a Km of 0.119 mM and a Vmax of 0.313 U.Keywords: Lachnocladium sp., anion exchange chromatography, gel filtration chromatography, ABTS, DM

Comparison of paracetamol pharmacokinetics in Panadol® and Panadol extra®

The influence of caffeine (60mg) was studied on the pharmacokinetic characteristics of paracetamol (1000mg single dose) in six healthy male human volunteers. A double beam spectrophotometer was used to analyse salivary paracetamol concentrations. Caffeine caused a significant (p< 0.05) decrease in the saliva concentration of paracetamol (C ) and area under salivary paracetamol concentration curve (AUC). There was no statistically significant increase in max elimination half-life (t ) and clearance (Cl) of paracetamol in man. There was statistically significant increase in half 1/2el life of absorption of paracetamol (t ) from Panadol Extra®. The results indicated impaired absorption of paracetamol 1/2abfrom Panadol Extra®

Quality control of some brands of chloroquine tablets available in Nigeria

The aim of this study is to examine the quality of twenty brands of chloroquine tablets available in Nigeria. The identification, assay and in vitro studies of twenty (A-T) commercial brands of chloroquine tablets readily available in Nigeria were examined using official methods. All the brands passed the uniformity of weight test and the chemical identification tests. Their infra red (IR) spectra patterns were similar to that of reference sample. Brands F and H did not give any melting point. Only brand K failed the hardness test; 8 brands each out of twenty failed the friability and the assay test. The result of brands E and K did not comply with the specification for disintegration of tablet in the monograph. The dissolution test results for all the brands except F and H were in conformity with the specification in British Pharmacopoeia (BP). Only five brands out of twenty brands examined passed all the tests that were carried out. The results therefore indicated that most brands of Chloroquine tablets in the market are not of good qualit

CYP2B6*6 genotype specific differences in artemether‐lumefantrine disposition in healthy volunteers

Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of the antimalarial drugs artemether and lumefantrine. Here we investigated the effect of&nbsp;CYP2B6*6 on the plasma pharmacokinetics of artemether, lumefantrine, and their metabolites in healthy volunteers. Thirty healthy and previously genotyped adult volunteers&mdash;15 noncarriers (CYP2B6*1/*1) and 15 homozygote carriers (CYP2B6*6/*6)&mdash;selected from a cohort of 150 subjects from the Ilorin metropolitan area were administered the complete 3‐day course of artemether and lumefantrine (80 and 480 mg twice daily, respectively). Intensive pharmacokinetic sampling was conducted at different time points before and after the last dose. Plasma concentrations of artemether, lumefantrine, dihydroartemisinin, and desbutyllumefantrine were quantified using validated liquid chromatography&ndash;mass spectrometric methods. Pharmacokinetic parameters were evaluated using noncompartmental analysis. Artemether clearance of&nbsp;CYP2B6*6/*6&nbsp;volunteers was nonsignificantly lower by 26% (ratios of geometric mean [90% CI]; 0.74 [0.52‐1.05]), and total exposure (the area under the plasma concentration‐time curve from time 0 to infinity [AUC0‐&infin;]) was greater by 35% (1.35 [0.95‐1.93]) when compared with those of&nbsp;*1/*1&nbsp;volunteers. Similarly, assuming complete bioconversion from artemether, the dihydroartemisinin AUC0‐&infin;&nbsp;was 22% lower. On the contrary, artemether‐to‐dihydroartemisinin AUC0‐&infin;&nbsp;ratio was 73% significantly higher (1.73 [1.27‐2.37]). Comparison of lumefantrine exposure and lumefantrine‐to‐desbutyllumefantrine metabolic ratio of&nbsp;*6/*6&nbsp;with corresponding data from&nbsp;*1/*1&nbsp;volunteers showed no differences. The increased artemether‐to‐dihydroartemisinin metabolic ratio of&nbsp;*6/*6&nbsp;volunteers is unlikely to result in differences in artemether‐lumefantrine efficacy and treatment outcomes. This is the first study in humans to associate&nbsp;CYP2B6*6&nbsp;genotype with artemether disposition.</p

Differential impact of nevirapine on artemether-lumefantrine pharmacokinetics in individuals stratified by CYP2B6 c.516G>T genotypes

There is an increased recognition of the need to identify and quantify the impact of genetic polymorphisms on drug-drug interactions. This study investigated the pharmacogenetics of the pharmacokinetic drug-drug interaction between nevirapine and artemether-lumefantrine in HIV-positive and HIV-negative adult Nigerian subjects. Thirty each of HIV-infected patients on nevirapine-based antiretroviral therapy and HIV-negative volunteers without clinical malaria, but with predetermined CYP2B6 c.516GG and TT genotypes, were administered a complete treatment dose of 3 days of artemether-lumefantrine. Rich pharmacokinetic sampling prior to and following the last dose was conducted, and the plasma concentrations of artemether/dihydroartemisinin and lumefantrine/desbutyl-lumefantrine were quantified using tandem mass spectrometry. Pharmacokinetic parameters of artemether-lumefantrine and its metabolites in HIV-infected patients on nevirapine were compared to those in the absence of nevirapine in HIV-negative volunteers. Overall, nevirapine reduced exposure to artemether and desbutyl-lumefantrine by 39 and 34%, respectively. These reductions were significantly greater in GG versus TT subjects for artemether (ratio of geometric mean [90% confidence interval]: 0.42 [0.29 to 0.61] versus 0.81 [0.51 to 1.28]) and for desbutyl-lumefantrine (0.56 [0.43 to 0.74] versus 0.75 [0.56 to 1.00]). On the contrary, it increased exposure to dihydroartemisinin and lumefantrine by 47 and 30%, respectively. These increases were significantly higher in TT versus GG subjects for dihydroartemisinin (1.67 [1.20 to 2.34] versus 1.25 [0.88 to 1.78]) and for lumefantrine (1.51 [1.20 to 1.90] versus 1.08 [0.82 to 1.42]). This study underscores the importance of incorporating pharmacogenetics into all drug-drug interaction studies with potential for genetic polymorphisms to influence drug disposition