Transcript Diapositivo 1

POPULATION PHARMACOKINETICS
OF ANTIRETROVIRAL DRUGS IN HCV/HIV
OR HBV/HIV CO-INFECTED INDIVIDUALS
J.P.
1,2
Cruz ,
D.
1
Matias ,
C.
1
Carvalho ,
J.
2
Morais ,
E.
3
Valadas ,
F.
3
Antunes
1) Pharmacology and Pharmacogenetics Laboratorial Unit, Laboratório de Diagnóstico Molecular de Doenças Infecciosas, Faculdade de Medicina da Universidade de Lisboa; 2)
iMed.UL – Research Institute for Medicines and Pharmaceutical Sciences; 3) Clinica Universitária de Doenças Infecciosas, Faculdade de Medicina da Universidade de Lisboa.
Results
Introduction and purpose
• The human immunodeficiency virus (HIV)
infection affects more than 40 million individuals
worldwide;
Table 1 – Study population charateristics.
• About one quarter of every HIV-infected individual
in developed world is also HCV infected and about
one tenth HIV-infected individuals are HBV infected.
These co-infections speed up liver disease
progression and HIV immune system deterioration;
• Drug efficacy is dependent on the amount of drug
available on site of action. Most antiretroviral drugs
are mainly metabolized by liver enzymes.
Consequently, the presence of liver disease can
influence their efficacy. Pharmacokinetics of
antiretroviral drugs in co-infected patients should
then be assessed;
• This study was designed to compare ajusted
bayesian pharmacokinetic parameters in co-infected
patients versus non co-infected patients.
Figure 1 – Study drug distribuition.
Table 2 – Adjusted bayesian pharmacokinetic parameters for non nucleoside reverse transcriptase inhibitors.
Table 3 – Adjusted bayesian pharmacokinetic parameters for protease inhibitors.
Methods
• 60 HIV-infected patients on triple antiretroviral
therapy from the Clinical Ward of Infectious Diseases
of Santa Maria Hospital (Lisbon) were enrolled;
• Blood samples were collected between 8 and 24
hours post-dose (trough concentration / Cmin) and
analyzed by an HPLC-UV validated method;
• Individual demographic and clinical data were
retrieved;
• Aboottbase PKS software was used to estimate
adjusted bayesian pharmacokinetic parameters
(clearance, volume of distribution, elimination rate
constant, half-life) and Cmin;
• All results were analyzed in IBM SPSS 17.0 by
Mann-Whitney (MW-test) or t-Student tests
(t-test) .
Discussion
• A clear association between hepatic enzymes (GPT, GOT, GGT) and co-infection was
found (p < 0,05). Also urea plasma levels showed correlation with the presence of viral
hepatitis (t-test, p = 0,009) (results not shown).
• The statistical analysis showed a significant difference in lopinavir Cmin (MW-test,
p < 0,05) with higher mean±SD Cmin values for co-infected patients (3953±679 ng/mL
versus 2383±1389 ng/mL).
• The adjusted bayesian pharmacokinetic parameters obtained showed no statistically
significant
differences
except
for
a
trend
in
lopinavir
half-life
(t-test, p = 0,07).
Conclusions
• This preliminary study reveals a small association between some adjusted bayesian pharmacokinetic parameters of antiretroviral drugs and the
presence of HCV or HBV co-infection in HIV-infected patients. The lopinavir Cmin was significantly influenced by the presence of viral hepatitis, however
the statistical association of the other adjusted lopinavir pharmacokinetic parameters was not so clear.
• To disclose further association between the presence of HIV-HCV or HIV-HBV co-infection and antiretroviral pharmacokinetics,
more robust data are needed.