Clin Pharmacokinet
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Uncertainty exists as to the most suitable pharmacokinetic parameter sets for propofol target-controlled infusions (TCI). The pharmacokinetic parameter sets currently employed are clearly not universally applicable, particularly when patient attributes differ from those of the subjects who participated in the original research from which the models were derived. Increasing evidence indicates that the pharmacokinetic parameters of propofol can be scaled allometrically as well as in direct proportion to lean body mass (LBM). ⋯ Simulations of TCI using improved equations to calculate LBM indicate that the Schnider model delivers similar amounts of propofol to morbidly obese patients as do the allometrically scaled pharmacokinetic parameter sets. These hypotheses deserve further investigation. To facilitate further investigation, researchers are encouraged to make their data freely available to the WorldSIVA Open TCI Initiative (http://opentci.org).
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During the newborn period and early infancy, renal function matures, resulting in changes in the glomerular filtration rate (GFR). This study was performed to quantify developmental changes in the GFR in (pre)term neonates by use of amikacin clearance as proof of concept. The model was used to derive a rational dosing regimen in comparison with currently used dosing regimens for amikacin. ⋯ Amikacin clearance, reflecting the GFR in neonates, can be predicted by birthweight representing the antenatal state of maturation of the kidney, postnatal age representing postnatal maturation, and co-administration of ibuprofen. Finally, the model reflects maturation of the GFR, allowing for adjustments of dosing regimens for other renally excreted drugs in preterm and term neonates.
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Review
The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically ill patients.
Low serum albumin levels are very common in critically ill patients, with reported incidences as high as 40-50%. This condition appears to be associated with alterations in the degree of protein binding of many highly protein-bound antibacterials, which lead to altered pharmacokinetics and pharmacodynamics, although this topic is infrequently considered in daily clinical practice. The effects of hypoalbuminaemia on pharmacokinetics are driven by the decrease in the extent of antibacterial bound to albumin, which increases the unbound fraction of the drug. ⋯ Dose adjustments of these antibacterials in critically ill patients with hypoalbuminaemia should be regarded as another step for antibacterial dosing optimization. Moreover, some of the new antibacterials in development exhibit a high level of protein binding although hypoalbuminaemia is rarely considered in clinical trials in critically ill patients. Further research that defines dosing regimens that account for such altered pharmacokinetics is recommended.
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Randomized Controlled Trial
A pharmacokinetic and pharmacodynamic study of oral oxycodone in a human experimental pain model of hyperalgesia.
Oxycodone is not as well characterized, with respect to its pharmacokinetic/pharmacodynamic properties, as other opioids. Moreover, the pharmacodynamic profile of oxycodone can be affected by changes in the pain system, e.g. hyperalgesia. Therefore, the aim of this study was to investigate the pharmacokinetic/pharmacodynamic profiles of oxycodone in a human experimental pain model of hyperalgesia. ⋯ There was a measurable effect of oxycodone, compared with placebo, on all pain measures, and a linear concentration-effect relationship without an effect delay was demonstrated. This could indicate an initial peripheral analgesic effect of oxycodone.
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The prevalence of obesity has dramatically increased in recent years and now includes a significant proportion of the world's children, adolescents and adults. Obesity is linked to a number of co-morbidities, the most prominent being type 2 diabetes mellitus. While many agents are available to treat these conditions, the current knowledge regarding their disposition in the obese remains limited. ⋯ This review also examines recent publications that investigated the disposition of several classes of drugs in the obese--antibacterials, anticoagulants, antidiabetics, anticancer agents and neuromuscular blockers. In conclusion, pharmacokinetic data in obese patients do not exist for the majority of drugs. In situations where such information is available, clinicians should design treatment regimens that account for any significant differences in the CL and V(d) in the obese.