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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)
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)
AIMS The aims of the study were a) to determine if there is evidence of saturable protein binding of cefazolin in plasma across the range of concentrations achieved clinically (between patient variability) and b) to investigate whether saturable protein binding is also evident from trough and peak concentrations in the same patient (within patient(More)
BACKGROUND Lithium is a well-established treatment for bipolar I disorder in adults. However, there is a paucity of information on its pharmacokinetics/pharmacodynamics in children and adolescents. We aimed to develop the first lithium dosage regimens based on population pharmacokinetics/pharmacodynamics for paediatric patients. METHODS Lithium(More)
Metformin therapy is limited in patients with chronic kidney disease (CKD) due to the potential risk of lactic acidosis. This open-label observational study investigated metformin and lactate concentrations in patients with CKD (n = 22; creatinine clearances 15-40 ml/min) and in two dialysed patients. Patients were prescribed a range of metformin doses(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)
AIMS Our aim was to identify and quantify the sources of variability in oxypurinol pharmacokinetics and explore relationships with plasma urate concentrations. METHODS Non-linear mixed effects modelling was applied to concentration-time data from 155 gouty patients with demographic, medical history and renal transporter genotype information. RESULTS A(More)
Of 73 wild and domestic mammals tested from an area endemic for pseudorabies in swine, 16 showed natural pseudorabies virus infection, 8 from farms with no pseudorabies history. In transmission experiments with swine and raccoons (Procyon lotor), pseudorabies was not transmitted between raccoons but was transmitted reciprocally between raccoons and swine by(More)
AIMS To explore the extent, time course, site(s), mechanism and possible clinical relevance of the pharmacokinetic (PK) interaction between piperacillin and flucloxacillin. METHODS A single-dose, randomized, six-way crossover study in 10 healthy volunteers where all subjects received all of the following as 5-min intravenous infusions: (i) 1.5 g(More)