ISSN:0312-5963    

出版商:ADIS    

年代:1987

数据来源: ADIS

摘要:

Of the neurological disorders, none can claim a battery of therapeutic agents based upon as rational a pharmacology as can Parkinson's disease. In this review, the clinical pharmacokinetics of the major classes of anti-Parkinsonian drugs is discussed. Although they are the oldest drugs in the anti-Parkinsonian armamentarium, little pharmacokinetic data are available regarding the anticholinergic and antihistaminic agents. Based on elimination half-lives of 10 to 18 hours, most could probably be effectively given on a twice-daily schedule. Amantadine is unique among anti-Parkinsonian agents both in lacking a clearly defined mechanism of action and in being eliminated from the body exclusively by renal excretion of unchanged drug. Thus the normal decline of renal function in the elderly Parkinsonian population becomes an important factor in avoiding potential drug toxicity. The pharmacokinetics and pharmacodynamics of levodopa are complex. Since it is an amino acid, it follows metabolic pathways and must compete for absorption and brain uptake with a number of large neutral amino acids. It has a short elimination half-life and, as Parkinson's disease progresses, the brain loses its capacity to store the drug and becomes dependent in a moment-to-moment fashion on plasma levodopa concentrations, creating therapeutic response fluctuations in over 50% of patients. Pharmacokinetic considerations in the management of these response fluctuations are discussed. The newest class of anti-Parkinsonian agents are the direct acting dopamine receptor agonists. These drugs, all derivatives of ergot, have more prolonged durations of anti-Parkinsonian action than levodopa. However, other than bromocriptine, clinical experience with members of this class of drugs is still limited.

ISSN:0312-5963    

出版商:ADIS    

年代:1987

数据来源: ADIS

摘要:

Pharmacokinetic profiles of the 1,4-substituted benzodiazepines are defined by their absorption, distribution, metabolism, and excretion characteristics. An ability to cross the blood-brain barrier and the onset of pharmacological activity have been associated with the physiochemical properties of the benzodiazepines. In addition, drug concentrations in the CSF correlate with the unbound drug concentrations in blood or plasma. Duration of pharmacological activity of the benzodiazepines in humans is associated with the affinity of these compounds for the benzodiazepine receptors in human brain. Therefore, benzodiazepines with high affinity for the benzodiazepine receptor sites in human brain tend to exhibit prolonged half-lives of elimination from the CSF which correlate with the prolonged duration of clinical and pharmacological effects and lower therapeutic doses of these drugsin vivo.

ISSN:0312-5963    

出版商:ADIS    

年代:1987

数据来源: ADIS

摘要:

The pharmacokinetics of lignocaine (lidocaine) and bupivacaine following epidural administration were studied in 12 surgical patients using a stable isotope method. Shortly after epidural administration of the agent to be evaluated, a deuterium-labelled analogue was administered intravenously. Plasma concentrations of the unlabelled and the deuterium-labelled local anaesthetics were determined using gas chromatography and mass fragmentography. The pharmacokinetic behaviour of both agents was consistent with a 2-compartment open model and two parallel first-order absorption processes. The mean distribution and elimination half-lives were 12 minutes and 100 minutes for lignocaine, and 22 minutes and 143 minutes for bupivacaine. The mean volumes of the central compartment and the mean steady-state volumes of distribution were: lignocaine, 43L and 99L; bupivacaine, 33L and 68L. Total plasma clearances averaged 0.95 L/min (57 L/h) for lignocaine and 0.52 L/min (31.2 L/h) for bupivacaine. The half-lives, characterising the fast and slow absorption processes, were 9.3 and 82 minutes for lignocaine, and 7.0 minutes and 362 minutes for bupivacaine; the fractions of the doses absorbed in the fast and slow processes were lignocaine 0.38 and 0.58, bupivacaine 0.28 and 0.66, respectively. The results indicate that the local anaesthetics are completely absorbed from the epidural space into the general circulation. The initial absorption rates of both local anaesthetics appear to be similar, but, later, the absorption of bupivacaine proceeds much more slowly than the absorption of lignocaine.

ISSN:0312-5963    

出版商:ADIS    

年代:1987

数据来源: ADIS