title: False Prolongation of Prothrombin Time in the Presence of a High Blood Concentration of Daptomycin.
abstract: 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.
authors.affiliation: Department of Pharmacy, Osaka Medical College Hospital, Takatsuki, Osaka, Japan. phc032@osaka-med.ac.jp.|Infection Control Center, Osaka Medical College Hospital, Takatsuki, Osaka, Japan. phc032@osaka-med.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Laboratory of Cardiovascular Pharmacology and Toxicology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.affiliation: Department of Pharmacy, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Clinical Laboratory, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.
authors.forename: Hidema
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Pharmacy, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Laboratory of Cardiovascular Pharmacology and Toxicology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ijiri
authors.affiliation: Department of Clinical Laboratory, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ikemoto
authors.affiliation: Department of Pharmacy, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nishihara
authors.affiliation: Laboratory of Cardiovascular Pharmacology and Toxicology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.|Department of Internal Medicine III, Osaka Medical College, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Kidney Center, Shirasagi Hospital, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Osaka Medical College, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamai
authors.affiliation: Infection Control Center, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ukimura
authors.affiliation: Department of Pharmacy, Osaka Medical College Hospital, Takatsuki, Osaka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Katsumata
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001778:Blood Coagulation Disorders / Q000097:blood / Q000175:diagnosis; D002626:Chemistry, Pharmaceutical; D017576:Daptomycin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D003951:Diagnostic Errors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008081:Liposomes; D008954:Models, Biological; D009010:Monte Carlo Method; D009994:Osmolar Concentration; D014677:Pharmaceutical Vehicles / Q000032:analysis / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000097:blood / Q000737:chemistry; D011517:Prothrombin Time; D015203:Reproducibility of Results
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D014677:Pharmaceutical Vehicles; D010715:Phosphatidylglycerols; C084352:distearoyl phosphatidylglycerol; D017576:Daptomycin; C030345:1,2-dipalmitoylphosphatidylglycerol