False Prolongation of Prothrombin Time in the Presence of a High Blood Concentration of Daptomycin
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- 作者：Tomoyuki Yamada ; Ryuji Kato ; Kazutaka Oda ; Hidema Tanaka ; Kaoru Suzuki ; Yoshio Ijiri ; Toshiyuki Ikemoto ; Masami Nishihara ; Tetsuya Hayashi ; Kazuhiko Tanaka ; Hiroshi Tamai ; Akira Ukimura and Takahiro Katsumata
- 刊名：Basic & Clinical Pharmacology & Toxicology
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：119
- 期：4
- 页码：353-359
- 全文大小：190K
- ISSN：1742-7843
文摘
Prothrombin time (PT) can reportedly be falsely prolonged by the antimicrobial drug daptomycin (DAP), and concomitant use of phosphatidylglycerol (PG). Although high doses of DAP (>6 mg/kg/day) are recommended for severe infection and result in a high blood concentration, the extent to which high blood concentrations of DAP interfere with PT, in the presence or absence of PG, has yet to be determined when using the HemosIL RecombiPlasTin 2G (Werfen Japan, Tokyo, Japan). We examined the effects of high doses of DAP on PT using this reagent. DAP (0–500 mg/L) was added to normal plasma and plasma with an already prolonged PT in the presence or absence of liposomal amphotericin B (L-AMB, 5–50 mg/L) or COATSOME EL-01 empty cationic liposomes (CS, 25–250 mg/L). Furthermore, we undertook a Monte Carlo simulation to calculate the probability of achieving DAP concentrations >100, >200 and >500 mg/L 0–48 hr after administering 6–12 mg/kg of DAP. Apparent PT increased with increasing DAP concentration, but neither L-AMB nor CS appeared to further elevate PT when co-administered with DAP. The probability of achieving DAP concentrations >100 and >200 mg/L increased with DAP dose. Higher doses of DAP than the approved dose caused false prolongation of PT. PT should be monitored carefully in patients taking high doses of DAP; ideally, PT should be measured at the trough blood concentration of DAP. Concomitant use of L-AMB and CS did not generally further elevate PT when co-administered with DAP.