Inter-individual Variability of Once Daily Ritonavir Boosted Saquinavir
Pharmacokinetics in Thai and UK Patients
Differential
exposure to saquinavir/ritonavir
may lead to therapy failure.
The objective of this joint Thai-UK study was to identify factors
that influence variability of saquinavir/ritonavir plasma
concentrations.
Saquinavir/ritonavir
data were pooled from 3 separate pharmacokinetic
studies in which the 2 drugs were dosed 1600/100
mg once
daily, respectively, in 45 patients
from Thailand and the UK.
Pharmacokinetic
parameters were based on non-compartmental analysis.
Univariate
analysis was performed with saquinavir as the dependent
variable, and ritonavir (Norvir)
area under the curve (AUC), gender, body weight, body
mass index (BMI) and study site as independent variables.
Results
Higher saquinavir
AUCs, maximum concentrations (Cmax) and
minimum concentrations (Cmin) were seen in Thai
patients than in UK
patients.
Univariate
analysis showed associations between body weight, gender,
study site and ritonavir AUC and saquinavir AUC (P
< 0.05), whereas BMI (P = 0.13) did not.
In
multivariate analysis, ritonavir AUC (P = 0.0001) and
study site (P = 0.0021) were significantly related
to saquinavir AUC (R2 = 0.50).
The
ritonavir AUC and study site appeared to be related
to exposure of saquinavir, according ot the authors. They concluded,
“Study site should be viewed as the total of country-
and study-specific differences—such as differences
in lifestyle, environment, genetic background, and
dietary composition—between the analyzed studies.”
10/24/05
Reference
Inter-individual variability of once-daily ritonavir boosted saquinavir pharmacokinetics
in Thai and UK patients. The Journal of Antimicrobial
Chemotherapy 56(5): 908-913. November 2005.
