TDM in Ugandan study highlights importance of refridgerated ritonavir

Therapeutic Drug Monitoring (TDM) is usually considered as an additional luxury for some resource rich settings, but a study presented by Ceppie Merry highlighted how pharmacokinetic studies may have a particular importance in confirming likely treatment efficacy in different populations and settings to the original clinical trials.

In a nested sub-study of 18 patients treated in a programme that is providing ARV treatment in Uganda, Kenya, Ivory coast and Senegal, drug levels of hard gel saquinavir (hgc SQV, Invirase), soft gel saquinavir (sgcSQV, Fortovase) and ritonavir (RTV). The once-daily regimens used 1600mg or either formulation of saquinavir with 100mg ritonavir.

Boosted Invirase demonstrated less interpatient variability and a greater proportion of patients with therapeutic trough concentrations. Of concern, half of the samples showed ritonavir concentrations below the limit of detection of the assay (<10ng/mL) at some point during the 24-hour dosing period.

The study observed that observed dosing meant that adherence could not explain these levels, but that poor ritonavir storage could. A previous quality control analysis of drugs sourced in Africa found both SQV formulations contained drug content to USP standards but the ritonavir levels were 16-19% lower than stated in the label.

Merry C, Coakely C, Kityo C et al. Pharmacokinetics (PK) of saquinavir and ritonavir in Ugandan patients receiving ritonavir-boosted saquinavir hard and soft gel. 7th ICDTHI,14-18 Nov, 2004, Glasgow. Abstract P277.