Fig 1.
CONSORT Flow Diagram for trial.
Fig 2.
The raltegravir-raltegravir glucuronide (parent-metabolite) compartment model.
N1 denotes the first hypothetical transit compartment up to Nn compartment. ktr is the transit rate constant. ka is the absorption rate constant from the hypothetical drug depot compartment to plasma. CL/V (or k) is the elimination rate constant of raltegravir. FMET is the fraction of raltegravir clearance for the formation of raltegravir glucuronide. VM, the distribution volume of the metabolite, was fixed to 1. As such, FMET is estimated as the ratio of the formation rate of glucuronide to VM. CLM is the glucuronide clearance.
Table 1.
ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; wt, wild-type genotype; het, heterozygous variant genotype; var, homozygous variant genotype.
Table 2.
Final pharmacokinetic parameter estimates for the raltegravir-metabolite model.
Fig 3.
Scatterplot and linear correlation between nadir absolute neutrophil count (ANC) and rate constant of formation of raltegravir glucuronide from raltegravir (K23).
The regression equation is ANC = 129.2 + 89461.5*K23. R is 0.598 (p = 0.00158).
Fig 4.
Box-plot showing the association between the rate constant of formation of raltegravir glucuronide from raltegravir (K23) and presence or absence of dose delay amongst the patients.
Fig 5.
Box-plots showing the statistically insignificant associations between the nadir absolute neutrophil count and UGT1A1 genotypes.