Pharmacokinetics and 48-week safety and efficacy of generic ritonavir tablet-boosted atazanavir in HIV-1-infected Thai adults.

BACKGROUND: Ritonavir (RTV) tablets were not available in Thailand until they were manufactured by the Government Pharmaceutical Organization of Thailand. We assessed pharmacokinetics (PK), safety and efficacy of generic RTV-boosted atazanavir (ATV) in virologically suppressed HIV-1-infected Thai adults. METHODS: Virologically suppressed HIV-1-infected Thai adults who currently use ATV (either 200 or 300 mg) with Norvir® soft gel capsule (SGC) 100-mg-based regimen were enrolled into this prospective, 48-week single-arm study. Participants switched from Norvir® SGC to generic RTV. Plasma trough concentration (Ctrough) was assessed at baseline before switching to generic RTV and week 24 in all participants, with the target ATV Ctrough of 0.15 mg/l. Plasma HIV-1 RNA and other laboratory safety parameters were assessed until week 48. RESULTS: Of 100 participants (51% male) enrolled, 50% was using ATV 200 mg and 50% was using 300 mg at the time RTV SGC were changed into generic tablets. All participants used two nucleoside reverse transcriptase inhibitors (NRTIs) as backbone. There were no significant changes in mean (sd) Ctrough of RTV (0.20 [0.33] versus 0.23 [0.39]; P=0.21) and ATV (0.83 [0.93] versus 0.88 [0.95]; P=0.62) between baseline and week 24. From entry to week 48, median alanine aminotransferase significantly increased from 25 to 30 IU/l (P=0.001) and total bilirubin significantly decreased from 1.7 to 1.3 (P=0.04). One study drug related grade 3 adverse event was reported. All but one participant maintained plasma HIV-1 RNA <50 copies/ml after 48 weeks. CONCLUSIONS: Generic RTV-boosted ATV showed adequate levels, good tolerability and great efficacy after 48 weeks.

The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity.

Since the major approach in searching for potential anticancer agents over the last 50 years has been based on selective cytotoxic effects on mammalian cancer cell lines, cell-based methods for cytotoxicity are described and compared. The sulphorhodamine B (SRB) assay is described in detail as the preferred method and also a novel approach has been developed which is based on the hypothesis that, in some circumstances, the naturally occurring compounds act as prodrugs rather than active compounds in their own right. Consequently, extracts or compounds are pre-incubated with systems modelling metabolic processes in the body before being tested. The methods have been validated using known compounds and Iris tectorum extracts have been shown to be more cytotoxic after treatment with beta-glucosidase. In addition bioassays based on mammalian cells involving antioxidant and upregulation of some cellular self-defence mechanisms are discussed which are related to prevention as well as treatment of cancer. Extracts of Alpinia officinarum induced glutathione-S-transferase (GST) activity in cultured hepatocytes and this was traced to the phenylpropanoids present, especially 1'-acetoxychavicol acetate.