Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
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Doripenem pharmacokinetics in critically ill patients receiving continuous hemodiafiltration (CHDF).
Objectives of the prospective, open-label study were to investigate pharmacokinetics of doripenem and determine appropriate doripenem regimens during continuous hemodiafiltration (CHDF) in critically ill patients with renal failure (creatinine clearance <30 ml/min) in the intensive care unit at a university hospital in Japan. Six patients received intravenous (IV) administration of 250 mg of doripenem every 12 or 24 hours during CHDF (dialysis rate, 500 ml/h; hemofiltration rate, 300 ml/h) via a polysulfone hemofilter. Doripenem concentrations in pre- and post-membrane blood (plasma) samples collected at specified times during one dosing interval were measured in order to calculate pharmacokinetic parameters and clearance via hemodiafiltration. ⋯ An IV dose of 250 mg of doripenem every 12 hours during CHDF provided adequate plasma concentrations for critically ill patients with renal failure, without resulting in accumulation upon steady-state. Thus, under the conditions tested, CHDF appeared to have little effect on doripenem clearance. Therefore, the blood level of doripenem can be satisfactorily controlled by adjustment of doripenem dose and dosing interval, in accordance with residual renal function in patients receiving CHDF.
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The purpose of this study was to evaluate the incompatibility of ceftriaxone sodium with calcium-containing products using the ionic product of precipitation, and the measurement of insoluble microparticles using a light obscuration particle counter. Appropriate volumes of 2% (w/v) calcium chloride solution were added to 0.4-2 mg/ml ceftriaxone isotonic sodium chloride solution, to make solutions with a final calcium ion concentration of 1.25 mmol/l. The solutions were gently agitated and stored at 37 degrees C for 24 h. ⋯ The numbers of insoluble microparticles in sample solutions made by adding calcium chloride to the sample were significantly higher than those made by adding calcium gluconate. These results suggest that ceftriaxone should not be co-administered with calcium-containing products even if no precipitation is observed visually. There will still be insoluble microparticles caused by incompatibility in the sample solution when the Saturation Index of the solution is over 1.0.