Browsing by Author "Masimirembwa, Collen M."

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    Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics of praziquantel in rats.
    (1992-06-25) Masimirembwa, Collen M.; Naik, Yogeshkumar S.; Hasler, Julia A.
    The effects of phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment on the phannac~kinetics of praziquantel (PZQ), a schistosomicide were studied in Spnrgue-Dawley rats. Blood samples at different time intervals were obtained by severing the tail vein and were analyzed for unchanged PZQ by HPLC. The PB-pretreated rats showed a &fold decrtase in AUC, a 5-fold decrease in Cmax and an 8-fold increase in Ch compared to the saline treated controls. The MC-pretreated rats and their oliveoil treated controls did not show any statistically significant diffmnces in the above parameters. These results suggest that PZQ is extensively metabolised by PB-inducible cytochrome P-450 isoforms and not by MC-inducible isoforms. These findings also suggest that the bioavailability of praziquantel could be altered to a significant extent in humans taking drugs that are phenobarbital type inducers.
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    Phenotyping of the glutathione S-transferase M1 polymorphism in Zimbabweans and the effects of chloroquine on blood glutathione S-transferases M1-A
    (Elsevier, 1997-05-31) Mukanganyama, Stanley; Masimirembwa, Collen M.; Naik, Yogeshkumar S.; Hasler, Julia A.
    The frequency of the null allele phenotype of glutathione S-transferase (GST) M1 was investigated in 114 Zimbabweans and results for a subset of 63 subjects were compared with genotyping by PCR. In addition, the effect of the antimalarial chloroquine on blood levels of GSTMl and GSTA in 19 subjects was studied. Quantification of GSTs was by enzyme linked immunosorbent assays (ELISA). Thirty percent of the subjects were of the GSTMl null phenotype. Comparison of results of phenotyping by ELISA and genotyping by PCR showed that 16% of samples were in discordance; unknown mutations in the GSTMl gene in the Zimbabwean population may explain this observation. Chloroquine decreased levels of blood GSTM1 and GSTA by 50% or more. In populations treated with chloroquine, these decreases in GST activities might lead to compromised ability to detoxify xenobiotics, could confound GSTMl phenotyping and might invalidate use of GSTA as an indicator of liver damage. O 1997 Elsevier Science B.V. Keywords: Glutathione S-transferases; Phenotype; Black Zimbabweans; Chloroquine