ABSTRACT
In critically ill patients, drug exposure may be influenced by altered drug distribution and clearance. Earlier studies showed that the variability in caspofungin exposure was high in intensive care unit (ICU) patients. The primary objective of this study was to determine if the standard dose of caspofungin resulted in adequate exposure in critically ill patients. A multicenter prospective study in ICU patients with (suspected) invasive candidiasis was conducted in the Netherlands from November 2013 to October 2015. Patients received standard caspofungin treatment, and the exposure was determined on day 3 of treatment. An area under the concentration-time curve from 0 to 24 h (AUC0-24) of 98 mg · h/liter was considered adequate exposure. In case of low exposure (i.e., <79 mg · h/liter, a ≥20% lower AUC0-24), the caspofungin dose was increased and the exposure reevaluated. Twenty patients were included in the study, of whom 5 had a positive blood culture. The median caspofungin AUC0-24 at day 3 was 78 mg · h/liter (interquartile range [IQR], 69 to 97 mg · h/liter). A low AUC0-24 (<79 mg · h/liter) was seen in 10 patients. The AUC0-24 was significantly and positively correlated with the caspofungin dose in mg/kg/day (P = 0.011). The median AUC0-24 with a caspofungin dose of 1 mg/kg was estimated using a pharmacokinetic model and was 114.9 mg · h/liter (IQR, 103.2 to 143.5 mg · h/liter). In conclusion, the caspofungin exposure in ICU patients in this study was low compared with that in healthy volunteers and other (non)critically ill patients, most likely due to a larger volume of distribution. A weight-based dose regimen is probably more suitable for patients with substantially altered drug distribution. (This study has been registered at ClinicalTrials.gov under registration no. NCT01994096.).
Subject(s)
Antifungal Agents/administration & dosage , Echinocandins/administration & dosage , Echinocandins/pharmacokinetics , Lipopeptides/administration & dosage , Lipopeptides/pharmacokinetics , Adult , Aged , Aged, 80 and over , Antifungal Agents/pharmacokinetics , Area Under Curve , Candida albicans/drug effects , Candidiasis, Invasive/drug therapy , Caspofungin , Critical Illness , Echinocandins/therapeutic use , Female , Fluconazole/pharmacology , Fluconazole/therapeutic use , Humans , Intensive Care Units , Lipopeptides/therapeutic use , Male , Middle AgedABSTRACT
OBJECTIVE: To determine whether a double dose of intraarticular triamcinolone acetonide is more effective for knee arthritis than a 40-mg dose. METHODS: In this 12-week randomized controlled clinical trial, 40 mg and 80 mg of intraarticular triamcinolone acetonide were compared in patients with knee arthritis. Evaluated variables included a Likert burden scale, visual analog scale pain scale, degree of arthritis activity, presence of swelling, and presence of functional limitation. RESULTS: Ninety-seven patients were randomized. No significant differences were observed between the groups regarding any outcomes. CONCLUSION: An 80-mg dose of triamcinolone acetonide had no additional benefit compared with 40 mg as treatment for knee arthritis. TRIAL REGISTRATION: Nederlands Trial Register; trial registration number: NTR2298.
