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HIV/AIDS: Population PK/PD modelling of antiretroviral drug therapy

Although better drugs against HIV/AIDS are becoming more available, dosages may not always be optimal with respect to effectiveness, safety, administration convenience or cost. This project aims to quantitate the pharmacological relationship between dosing history, sources of variation between individuals, drug exposure, response and treatment outcome also taking into consideration the effects of co-infections such as TB and malaria.

Use of mixed effects modelling allows the analysis of multiple pharmacogenetic and demographic covariates in a pharmacokinetic population model, explaining between-subject variability. Several polymorphic genes coding for drug metabolizing enzymes and transporters were found to have effect on the disposition of the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz in healthy Ugandan subjects after single dose administration.

Moreover, using simulation it was demonstrated that a 35% dose reduction in HIV-positive Zimbabwean patients with decreased metabolic capacity would maintain drug exposure within the therapeutic range after repeated oral administration.

In a typical HIV efficacy study large amounts of drug response data are collected. However, traditionally only limited amounts of the recorded data are actually used for eliciting differences between regimens. We are seeking to develop a template drug-disease model integrating CD4-cell counts, HIV-RNA levels and drug concentrations.

 

Contact Information

Michael Ashton

Box 431 , 405 30 Göteborg

Visiting Address:
Medicinaregatan 13A

Phone:
+46 (0)31 786 34 12

Fax:
+46 (0)31 786 32 84

Page Manager: Webbredaktör|Last update: 3/13/2009
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