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Date of Award

1991

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Pharmacy

First Advisor

Paul Williams

First Committee Member

Donald Floriddia

Second Committee Member

David S. Fries

Third Committee Member

Donald Shirachi

Abstract

An evaluation of vancomycin pharmacokinetics was performed in 2 phases. In phase I, a vancomycin population pharmacokinetic model was developed based on data from 126 patients using a two-compartment model. Variables tested for inclusion in the model were creatinine clearance (Crcl), age, total body weight (wt) ICU status, gender, body surface area, ideal weight and height. Variables were included at the P < _ 0. 05 level. The final population pharmacokinetic model was as follows: Cl (L/hr) = (0.025 * Crcl) * (1 + 0.0165 *age), V1 (L) = 29.5, V2 (L) = 8.17 + 0.349 * Crcl and Q (L/hr.kg) = 0. 0639 * wt. For ICU patients, V2 was larger than the non ICU patients and it was V2 (L) = 16.258 + 0.694 * Crcl.

In phase II, the performance of the derived model was evaluated and compared to the Moellering, Matzke, Birt & Chandler and Rodvold Methods. Predictability of .52 vancomycin serum concentrations was assessed in 3 0 new patients. In predicting all concentration types, mean prediction error (MPE) with 95% CI for Moellering,. Matzke, Birt & Chandler, Rodvold and current methods were -0.1 (-1.6, 1.4), -0.8 (-0.7, 2. 4) , o. o ( -1.5, 1. 6) , -2. 0 ( -3. 4, -o. 5) , and 2. 1 ( o. 9, 3. 4) mg/L respectively. When considering only troughs, MPE with 95% CI were 1.8 (0.2, 3.4), 2.7 (0.9, 4.6), -1.5 (-3.5, 0.5), -1.5 (-3.2, 0.1), and 0.8 (-0.8, 2.4) mg/L respectively. MPE with 95% for the peaks were -2.5 (-5.0, 0.0), -1.6 (-4.1, 1.0), 2.0 (-0.4, 4.4), -2.5 (-5.3, 0.3) and 3.8 (1.8, 5.8) mg/L respectively.

Median absolute prediction error (MABPE) , 5% and 95% quantiles for all concentration types for Moellering, Matzke, Birt & Chandler, Rodvold and current methods were 3.4 (0.2, 10.1), 4.1 (0.3, 10.9), 3.9 (0.4, 11.7), 3.1 (0.2, 13.0) and 2.3 (0.1, 9.5) mg/L respectively. MABPE, 5% and 95% quantiles for the troughs were 2. 6 ( o. 2, 9. 4) , 4. o ( o. 4, 10. 3) , 4. 1 (0.7, 10.2), 2.9 (0.2, 9.4) and 2.0 (0.1, 9.2) mg/L respectively. MABPE, 5% and 95% quantiles for the peaks were 5.0 (0.7, 11.5·), 4.2 (0.3, 10.9), 3.8 (0.4, 11.7), 4.9 (0.6, 13.0) and 5.0 (1.1, 9.5) mg/L respectively.

It is recommended that the current method be used while setting initial target peak at 30 mg/L with the initial target trough at 6 mgjL. This should frequently result in serum vancomycin concentration within the therapeutic window. Individualization of therapy should then be done when the measured concentrations are available.

Pages

193

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