A pharmacokinetic and clinical evaluation of antimicrobial drugs in critically ill patients during Continuous Venovenous Haemodifiltration (CVVHDF) therapy
Citation:Almath M. Spooner, 'A pharmacokinetic and clinical evaluation of antimicrobial drugs in critically ill patients during Continuous Venovenous Haemodifiltration (CVVHDF) therapy', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2007, pp 371
Spooner TCD THESIS 8295 A pharmacokinetic.pdf (PDF) 184.4Mb
Critically ill patients are at risk from sepsis requiring antimicrobial therapy and acute renal failure, which may require extracorporeal renal replacement therapy. The objective of this study was to quantify and assess the impact of Continuous Venoveonous Haemodiafiltration (CVVHDF) therapy, a form of continuous renal replacement therapy, on the pharmacokinetics of commonly prescribed antimicrobial drugs. A preliminary audit undertaken as the first stage of this research identified a requirement for pharmacokinetic studies of a number of anti-infective agents during CVVHDF therapy. Two research strategies were used to address this objective. Initially a retrospective pharmacokinetic analysis of routinely monitored drug serum concentrations for patients treated with CVVHDF was used to obtain individual patient estimates of drug pharmacokinetic parameters. The drugs analysed were amikacin, gentamicin and vancomycin. Estimates of pharmacokinetic parameters obtained from the retrospective study of vancomycin agreed closely with published values from small prospective studies of vancomycin pharmacokinetics during Continuous Renal Replacement Therapy. In order to investigate drug disposition during CVVHDF further, a prospective pharmacokinetic and clinical study of antimicrobial drug therapy during CVVHDF was designed and implemented. In addition to examining routinely monitored antimicrobial drugs, an assay for ciprofloxacin determination in serum and CVVHDF effluent fluid was developed for the purposes of the prospective pharmacokinetic study. Ciprofloxacin differed from the other antibiotics examined, in that it has a significant non-renal component to its elimination. The prospective study allowed the measurement of multiple serum drug concentrations in a dosage interval and effluent fluid drug concentrations. Current drug dosing strategies for patients treated with CVVHDF were evaluated on the basis of these retrospective and prospective analyses. Both studies demonstrated significant drug clearance by CVVHDF. The retrospective study indicated that failure to adjust dosage regimens to account for this increased clearance capacity resulted in sub-therapeutic dosing of aminoglycoside antibiotics. The prospective study allowed analysis of the contribution of CVVHDF to total body clearance of each drug and an assessment of the validity of using therapeutic drug monitoring data to estimate pharmacokinetic parameters during CVVHDF.
Author: Spooner, Almath M.
Advisor:Corrigan, Owen I.
Publisher:Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences
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Type of material:thesis
Availability:Full text available