Carl M. J. Kirkpatrick

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Metformin is widely used for the treatment of type 2 diabetes mellitus. It is a biguanide developed from galegine, a guanidine derivative found in Galega officinalis (French lilac). Chemically, it is a hydrophilic base which exists at physiological pH as the cationic species (>99.9%). Consequently, its passive diffusion through cell membranes should be very(More)
OBJECTIVES To compare the plasma and subcutaneous tissue concentration-time profiles of meropenem administered by intermittent bolus dosing or continuous infusion to critically ill patients with sepsis and without renal dysfunction, and to use population pharmacokinetic modelling and Monte Carlo simulations to assess the cumulative fraction of response(More)
BACKGROUND Although QT prolongation is associated with increased risk of torsade de pointes (TdP), the precise relationship is not well defined. AIM To evaluate the performance of a QT nomogram in assessing the risk of TdP from QT-RR combinations. DESIGN Systematic review. METHODS We systematically searched MEDLINE/EMBASE for cases of drug-induced(More)
OBJECTIVES To perform a systematic review comparing the diagnostic accuracy of CysC with SCr. METHODS MEDLINE and EMBASE (January 1984-February 2006) were searched. Studies included i) evaluated CysC against a recognised 'gold standard' method for determining GFR using a receiver operating characteristics (ROC) curve analysis and ii) included data that(More)
The objectives of this study were (i) to compare the plasma concentration-time profiles for first-dose and steady-state piperacillin administered by intermittent or continuous dosing to critically ill patients with sepsis and (ii) to use population pharmacokinetics to perform Monte Carlo dosing simulations in order to assess the probability of target(More)
OBJECTIVES The goal of this study was to determine the bioactivity of urocortin (Ucn) in experimental heart failure (HF). BACKGROUND Urocortin may participate in cardiovascular function and pressure/volume homeostasis. Its effects in HF are unknown. METHODS Eight normal sheep and eight sheep with pacing-induced HF received ovine Ucn (10, 50, and 100 mg(More)
AIMS To review the basis and optimal use of therapeutic drug monitoring of antimicrobial agents. METHODS Antimicrobial agents for which a reasonable case exists for therapeutic drug monitoring are reviewed under the following headings: pharmacokinetics, why monitor, therapeutic range, individualization of therapy, sampling times, methods of analysis,(More)
Days to positivity in automated liquid mycobacterial culture have been shown to correlate with mycobacterial load and have been proposed as a useful biomarker for treatment responses in tuberculosis. However, there is currently no quantitative method or model to analyze the change in days to positivity with time on treatment. The objectives of this study(More)
The global epidemic of obesity has led to an increased prevalence of chronic diseases and need for pharmacological intervention. However, little is known about the influence of obesity on the drug exposure profile, resulting in few clear dosing guidelines for the obese. Here we present a semi-mechanistic model for lean body weight (LBW) that we believe is(More)
Drugs and metabolites are eliminated from the body by metabolism and excretion. The kidney makes the major contribution to excretion of unchanged drug and also to excretion of metabolites. Net renal excretion is a combination of three processes - glomerular filtration, tubular secretion and tubular reabsorption. Renal function has traditionally been(More)