|
Weight-related
Differences in the Pharmacokinetics of Abacavir in HIV Patients
The
aim of the current study was to study the possible influence
of patient characteristics on abacavir
(Ziagen) pharmacokinetics.
To achieve this, a population pharmacokinetic model for abacavir
was developed using data from 188 adult patients by the use of a
nonlinear mixed effects modeling method performed with NONMEM.
Results
Abacavir pharmacokinetics
was well described by a two-compartment open model with linear absorption
and elimination. Typical population estimates for the absorption
rate constant (Ka), the apparent central distribution volume (Vc/F),
the apparent peripheral distribution volume (Vp/F), the apparent
intercompartmental clearance (Q/F) and the apparent plasma clearance
(CL/F) were 1.8 h(-1), 75 l, 23.6 l, 10 l h(-1) and 47.5 l h(-1),
respectively.
Apparent plasma
clearance was positively related to body weight. Individual Bayesian
estimates of CL/F were used to calculate abacavir AUC. The latter
decreased from 10.7 +/- 5.0 to 5.7 +/- 1.6 mgh l(-1) when bodyweight
increased from 36 to 102 kg.
This drop in
abacavir exposure could lead to suboptimal treatment for the heaviest
patients, as antiviral efficacy of abacavir is known to be related
to its AUC.
A 400 mg abacavir
dose would be necessary to achieve adequate exposure to abacavir
in patients weighing more than 60 kg.
Conclusions
The authors
conclude, “The apparent plasma clearance of abacavir was positively
related to bodyweight. The efficacy of the current recommended abacavir
dosage for patients with high bodyweight
should be evaluated in further studies.”
Pharmacologie
Clinique, Universite Rene Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul,
Assitance Publique-Hopitaux de Paris, Paris, France.
02/02/05
Reference
V
Jullien and others. Weight related differences in the pharmacokinetics
of abacavir in HIV-infected patients. British Journal of Clinical
Pharmacology 59(2): 183-188. February 2005.
Link to Index of All HIV and AIDS
Articles by Topic
|
