Clin Pharmacokinet
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Review Comparative Study
Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19.
The isoenzymes which catalyse the polymorphic hydroxylations of debrisoquine/sparteine and S-mephenytoin are cytochromes P450 2D6 and P450 2C19 (CYP2D6 and CYP2C19), respectively. CYP2D6 is involved in the stereospecific metabolism of several important groups of drugs, for example antiarrhythmics, antidepressants and neuroleptics. About 7% of Caucasians but only 1% of Orientals are poor metabolisers (PMs) of debrisoquine. ⋯ As pronounced differences have been found between Caucasians and Orientals in the CYP2D6 and CYP2C19 enzymes, it might be expected that Black people will show even greater differences in this respect. Some studies have been performed with Black participants, but the picture is not clear. The mean CYP2D6 activity in Black EMs seems to be lower than that in Caucasian EMs and similar to that of Oriental EMs.(ABSTRACT TRUNCATED AT 400 WORDS)
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Remifentanil is a novel, short-acting mu-receptor opioid agonist currently in the late stages of development. A member of the 4-anilidopiperidine class, it is unique among the currently marketed agents because of its ester structure. Remifentanil undergoes widespread extrahepatic metabolism by blood and tissue nonspecific esterases, resulting in an extremely rapid clearance of approximately 3 L/min (180 L/h). ⋯ Speed of onset of effect is very rapid and is similar to that of alfentanil, which is reflected in a t1/2ke0 (a parameter used to characterise the delay between peak blood drug concentration and peak pharmacodynamic effect utilising a theoretical effect compartment) of approximately 1 to 2 minutes. Remifentanil is likely to be a welcome addition to the anaesthesia drug formulary. Anaesthetists have long recognised the need for a short-acting opioid with a predictable pharmacokinetic profile.(ABSTRACT TRUNCATED AT 400 WORDS)
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Bone infection has long been a formidable foe of orthopaedic surgeons. The standard method of treating osteomyelitis generally consists of irrigation and debridement supplemented by pre- and postoperative antibiotics and intraoperative antimicrobial solutions. In the 1970s, Buchholz introduced the concept of local antibacterial therapy in the form of antibiotic impregnated bone cement to treated infected arthroplasties. ⋯ This makes the use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads highly effective either as an alternative to, or in conjunction with, systemic antibiotic treatment of infected arthroplasties, and localised bone and soft tissue infection. This article explores the indications for the use of local therapy as well as any advantages or disadvantages it may have over systemic antibacterial treatment. Additionally, there are important pharmacokinetic considerations for the optimal use of antibacterial agents in the treatment of osteomyelitis.
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Burn injury induces many different pathological changes in the human body, which potentially alter pharmacokinetic parameters such as bioavailability, protein binding, volume of distribution (Vd) and clearance. The extent of these alterations depends on the drug, the type and extent of injury and the time that elapsed between injury and drug administration. Bioavailability of large and hydrophilic molecules may be increased because of enhanced intestinal permeability. ⋯ The therapeutic consequences of pharmacokinetic alterations are discussed in principle, and for specific treatment with antibacterials, anti-ulcer drugs, analgesics, muscle relaxants, anxiolytics, phenytoin and cyclosporin. If significant changes in pharmacokinetic disposition occur following thermal injury, therapeutic drug monitoring and dosage adjustment may be required to ensure rational and well tolerated drug therapy in patients with burns. Future studies should focus on the impact of specific patient variables (e.g. type of injury and size of burn) on the extent of pharmacokinetic alterations.
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Pain in childhood has not always been managed as actively as that in adults because of the limited amount of research available to provide guidelines for the management of paediatric pain. However, for many years now the pharmacokinetics and pharmacodynamics of opioid analgesics in infants and children have been studied intensively. Morphine is the standard for opioid analgesics and its pharmacology is the best studied in paediatric patients. ⋯ The high rate of drug metabolism means higher dosage requirements. In regard to the pharmacodynamics of opioid analgesics, infants and children do not appear to be more sensitive to the effects of opioids than adults. Thus, except for the neonatal period, the pharmacokinetics and pharmacodynamics of opioid analgesics are not markedly different from those of adults, and the risk of using opioids in infants and children is not higher.