title: Caspofungin exposure-response relationships in adult patients with mucosal or invasive candidiasis.
abstract: Caspofungin is an echinocandin antifungal agent administered once daily as an intravenous infusion. Relationships between caspofungin exposure and clinical efficacy and safety were investigated. End-of-infusion (CEOI ) and trough (C24 hours ) concentrations were obtained in 218 patients with mucosal (i.e., esophageal and/or oropharyngeal) candidiasis (MC) receiving caspofungin 35, 50, or 70 mg/day and 278 patients with invasive candidiasis (IC) receiving 50, 100, or 150 mg/day. Area under the plasma concentration-time curve (AUC0-24 hours ) was obtained in a subset of MC patients (n = 99). Odds ratios were estimated for the association between log-transformed PK and efficacy response and the occurrence of common adverse events. No pharmacokinetic or hybrid parameter (ratio of AUC:MIC, CEOI :MIC, C24 hours :MIC) was significantly correlated with overall treatment outcome in either MC or IC, although this patient population may exhibit confounding factors which masked a potential pharmacokinetic/pharmacodynamic relationship. An exploratory evaluation of MC identified significant pharmacokinetic correlations with endoscopic response, but not symptom response. Statistically significant associations were identified for IC patients with C. parapsilosis infections. Occurrence of clinical adverse events and/or laboratory abnormalities did not appear to be increased by higher caspofungin plasma concentrations. Caspofungin concentrations achieved with 50 mg/day are generally within the therapeutic window for the treatment of candidiasis.
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Comisar
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.|GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.|Johnson & Johnson, Wayne, PA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Li
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Sable
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Bi
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.|AstraZeneca LP, Wilmington, DE, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Chow
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Ngai
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Winchell
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kartsonis
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Stone
keywords: caspofungin; invasive candidiasis; mucosal candidiasis; pharmacodynamics; pharmacokinetics