AI Article Synopsis

  • - The study focuses on monitoring the drug levels of indinavir (IDV) in HIV-infected children who are also receiving ritonavir (RTV), evaluating how well these patients are absorbing the medication during treatment.
  • - Among 21 pediatric patients, those initially on a 250 mg/m² dose had low IDV levels, but most achieved adequate levels after increasing the dosage to 400 mg/m² plus RTV.
  • - Analysis revealed that patients with the C/C genotype (related to the MDR1 gene) had higher volume distribution for IDV, suggesting they may absorb the drug differently compared to those with the C/T or T/T genotypes, potentially leading to lower plasma levels in C/C genotype individuals. *

Article Abstract

The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clinical routine practice in HIV-infected children, whose antiretroviral treatment includes IDV boosted with ritonavir (RTV), and (2) describe a possible relationship between IDV pharmacokinetics and MDR1 genotypes. In 21 ambulatory pediatric patients receiving IDV plus RTV, IDV plasma levels and MDR1 genotypes on exon 26 (C3435T) were determined. Nine of the 21 patients initially receiving 250 mg/m(2) IDV yielded trough levels below 0.10 microg/ml (median: 0.21, range: 0.04-1.31 microg/ml). When the dosage was increased to 400 mg/m(2) IDV plus 100 mg/m(2) RTV b.i.d., all, except 1 patient, achieved levels above 0.10 microg/ml. Pharmacokinetic analysis showed higher volume of distribution median values related to the C/C genotype in comparison with C/T or T/T genotypes for exon 26 (4.57 vs. 1.20 and 1.50 l/kg, respectively; p = 0.002). Although a higher median value of clearance was observed with the C/C genotype, the difference was not statistically significant (1.43 vs. 0.27 and 0.42 l/h, respectively; p = 0.052). These results may be explained by a reduced absorption of the drug, related with lower plasma IDV levels in patients carrying the C/C genotype in exon 26.

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Source
http://dx.doi.org/10.1159/000178813DOI Listing

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