Background: A Phase II, multicentre, prospectively randomised, double-blind, parallel-group study was performed to investigate the dose response of micafungin at various dose levels in HIV positive patients with an endoscopically confirmed diagnosis of oesophageal candidiasis (OEC). The pharmacokinetics (PK) were also evaluated in a subset of patients in this study. Methods: This PK sub-study was performed at 13 sites in three countries; 9 in South Africa, 2 in Brazil, and 2 in Peru. Eligible patients were randomised 1:1:1 to 50, 100 or 150 mg/day micafungin. Plasma-concentration time profiles to define PK were collected on two occasions: after the first dose (Day 1) and after the last dose (End of Therapy). In addition to PK, a relationship between exposure and efficacy was also investigated. Results: Demographics: 45 Blacks, 21 Caucasians, 5 Mulattos, 2 Cape Coloureds and 1 Coloured. Mean age and weight were 37 years (range 19-68) and 54 kg (range 34-89) respectively. Micafungin exhibited linear PK over the dose range investigated. The half-life and clearance remained consistent with increasing dose. There was no accumulation of micafungin following repeated daily dosing for 14 or 21 days. Analysis of the relationship between systemic exposure and efficacy (defined as endoscopic clearance) showed the AUC0-24 on Day 1 was significantly correlated with efficacy response; with mean values of 74 Âµg.hr/mL in responders versus 38 Âµg.hr/mL in non-responders (p=0.0026). The mean AUC0-24 in the 50 mg treatment group (36 Âµg.hr/mL) was similar to that of the non-responders. In comparison, the corresponding values in the 100 and 150 mg treatment groups were 75 and 104 Âµg.hr/mL respectively. Conclusions: These data therefore suggest that a daily dose of between 100 and 150 mg would appear necessary to achieve the optimal exposure associated with a therapeutic response against oesophageal candidiasis in this patient population.
Full conference title:
47th Interscience Conference on Antimicrobial agents and Chemotherapy
- ICAAC 47th