|
KNUSTSpace >
Research Articles >
College of Agric and Natural Resources >
Please use this identifier to cite or link to this item:
http://hdl.handle.net/123456789/13518
|
Title: | Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis |
Authors: | Dompreh, Albert Tang, Xiaoli Zhou, Jianlin Yang, Hongmei Topletz, Ariel Ahwireng, Eugene Adu Antwi, Sampson Enimil, Antony Langaee, Taimour Peloquin, Charles A. Court, Michael H. Kwara, Awewura |
Keywords: | NAT2 acetylator genotypes SLCO1B1 gene CES2 gene single nucleotide polymorphisms rifampin pharmacokinetics isoniazid pharmacokinetics |
Issue Date: | 2017 |
Publisher: | Antimicrobial Agents and Chemotherapy |
Abstract: | Isoniazid and rifampin are essential components of first-line antituberculosis
(anti-TB) therapy. Understanding the relationship between genetic factors
and the pharmacokinetics of these drugs could be useful in optimizing treatment
outcomes, but this is understudied in children. We investigated the relationship between
N-acetyltransferase type 2 (NAT2) genotypes and isoniazid pharmacokinetics,
as well as that between the solute carrier organic anion transporter family member
1B1 (encoded by SLCO1B1) and carboxylesterase 2 (CES2) single nucleotide polymorphisms
(SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples
were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on
standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations
were determined by a validated liquid chromatography-tandem mass spectrometry
(LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental
analysis. Genotyping of NAT2, SLCO1B1, and CES2 SNPs were performed
using validated TaqMan genotyping assays. The Kruskal-Wallis test was used
to compare pharmacokinetic parameters among the three genotypic groups and
was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype
status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children
with a slow acetylator phenotype but not the rapid genotype. For rifampin,
only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics.
Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have
minimal clinical utility in dosing decisions at the population level in Ghanaian children,
but it could be useful at the individual level or in populations that have a high
frequency of implicated genotypes. Further studies in other populations are warranted. |
Description: | This article is published in Antimicrobial Agents and Chemotherapy |
URI: | http://hdl.handle.net/123456789/13518 |
Appears in Collections: | College of Agric and Natural Resources
|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
|