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Pharmacokinetic Characteristics of Bolus‐Administered Mannitol in Patients Undergoing Elective Craniotomy
Author(s) -
Kaneda Kotaro,
Baker Max T.,
Han TaeHyung,
Weeks Julie B.,
Todd Michael M.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009348973
Subject(s) - mannitol , pharmacokinetics , volume of distribution , medicine , anesthesia , population , dosing , bolus (digestion) , intravenous bolus , pharmacology , surgery , chemistry , environmental health , organic chemistry
To better understand mannitol pharmacokinetics, the authors constructed and compared population models for high‐ versus low‐dose bolus infusions in humans. Patients (aged 18–75, American Society of Anesthesiologists physical status 1–3) scheduled for elective craniotomy with an anticipated need for intraoperative mannitol were randomly assigned to receive either 0.5 (n = 10) or 1.0 (n = 12) g/kg of 20% mannitol over 15 minutes. Serial blood samples were collected at the predetermined intervals over 12 hours. Plasma mannitol concentrations were measured by gas chromatography and subjected to pharmacokinetic analysis; a 3‐compartment model best described mannitol disposition characteristics. Weight and dose were the important covariates for rapid peripheral volume of distribution (V2) and central clearance (CL1), respectively. Estimated population means were 2.80, 8.86, and 12.0 L for central (V1), rapid (V2), and slow (V3) volumes of distribution, respectively. Clearances of the central compartments (CL1) were 0.07 versus 0.04 L/min in the high‐ versus low‐dose group, respectively. Thus, mannitol kinetics can be considered as nonlinear. Clearances of the rapid peripheral (CL2) and slow peripheral compartments (CL3) were identical (2.07 and 0.16 L/min) in both. The current weight‐based dosing guidelines yielded greater than expected plasma drug concentrations in obese patients.