Clin Pharmacokinet
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Carboplatin shares some of the therapeutic advantages of cisplatin, but without a significant incidence of the dose-limiting neurotoxicity and nephrotoxicity which is experienced with cisplatin. However, its use is associated with dose-limiting bone marrow suppression. Carboplatin is present in the blood as 3 distinct species. ⋯ In adults, perhaps the most common method is that of Calvert which describes the relationship between dose and AUC. Paediatric formulas have also been described. More recently a number of limited sampling strategies have been proposed as well as Bayesian dose individualisation techniques.
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Review Comparative Study
Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences.
Hypercholesterolaemia plays a crucial role in the development of atherosclerotic diseases in general and coronary heart disease in particular. The risk of progression of the atherosclerotic process to coronary heart disease increases progressively with increasing levels of total serum cholesterol or low density lipoprotein (LDL) cholesterol at both the individual and the population level. The statins are reversible inhibitors of the microsomal enzyme HMG-CoA reductase, which converts HMG-CoA to mevalonate. ⋯ The best characterised statins from a clinical pharmacokinetic standpoint are fluvastatin and pravastatin. The major difference between these 2 compounds is the higher liver extraction of fluvastatin during the absorption phase compared with pravastatin (67 versus 45%, respectively, in the same dose range). Estimates of liver extraction in humans for lovastatin and simvastatin are poorly reported, which makes a direct comparison difficult.
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Mycobacterium avium complex (MAC) is an infrequent pulmonary pathogen in immunocompetent hosts. In patients with AIDS, MAC causes disseminated infection (DMAC) in up to 50% of those with CD4+ counts less than 100 cells/mm3. A significant portion of the total body burden of MAC is found inside macrophages, and the distribution of organisms has implications for drug therapy. ⋯ Patient-specific susceptibility data combined with therapeutic drug monitoring and dosage individualisation is one way to identify problems with drug therapy and to overcome them. Because many of the drugs used in patients with AIDS affect the metabolism of concurrently used drugs, therapeutic drug monitoring is a valuable asset for untangling multiple drug interactions. Since drug therapy is the only aspect of a mycobacterial infection within our control, the better we control the drug therapy, the better our patients should do.
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This paper presents an overview of the clinically relevant pharmacology of selective serotonin reuptake inhibitors (SSRIs) with an emphasis on their pharmacokinetics and effects on cytochrome P450 (CYP) enzymes. The SSRIs are potent inhibitors of the neuronal reuptake pump for serotonin (5-hydroxytryptamine; 5-HT) and have minimal effects on a number of other sites of actions (e.g. neuroreceptors and fast sodium channels). For this reason, drugs in this class have remarkable similarity as regards acute and maintenance antidepressant efficacy and tolerability profile. ⋯ Paroxetine substantially inhibits CYP2D6 but doses not appear to inhibit any other CYP enzyme. Sertraline produces mild inhibition of CYP2D6 but has little, if any, effect on CYP1A2, CYP2C9/10, CYP2C19 or CYP3A3/4. Understanding the similarities and differences in the pharmacology of SSRIs can aid the clinician in optimal use of this important class of antidepressants.
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Patients with renal insufficiency commonly require the administration of an opioid analgesic to provide adequate pain relief. The handling of morphine, pethidine (meperidine) and dextropropoxyphene in patients with renal insufficiency is complicated by the potential accumulation of metabolites. ⋯ Case reports of prolonged narcosis associated with the use of both codeine and dihydrocodeine in patients with renal insufficiency call for care to be used when prescribing these agents under such conditions. Although the pharmacokinetics of buprenorphine, alfentanil, sufentanil and remifentanil change little in patients with renal failure, the continuous administration of fentanyl can lead to prolonged sedation.