ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Veterinary and human pharmacology differ principally in the range of species in which drugs are used and studied. In animals, as in humans, an understanding of the dose-effect relationship can be obtained by linking pharmacokinetic behaviour with pharmacodynamic information. Studies of different classes of drugs support the assumption that the range of therapeutic plasma concentrations in animals is generally the same as in humans. The requirement for species differences in dosage or administration rate (dose/dosage interval) may be attributed to variations in pharmacokinetic behaviour or pharmacodynamic activity, or both. When administering a drug orally, the bioavailability from a dosage form can vary widely. This is particularly the case between ruminant animals (cattle, sheep and goats), horses and carnivorous species (dogs and cats). Species variations in bioavailability can be avoided by parenteral administration. Formulation of parenteral preparations and location of intramuscular injection site can, at least in horses and cattle, influence bioavailability.Comparative pharmacokinetic studies help to explain differences in absorption and disposition processes that may underlie species variations in response to fixed dosages of a drug. Certain marker substances are useful in quantifying the activity of metabolic pathways or efficiency of excretion processes. Prediction of preslaughter withdrawal times in food-producing animals represents an application of pharmacokinetics in the field of drug residues. The drug residue profile can be obtained by combining fixed dose pharmacokinetic studies with measurement of drug concentrations in selected tissues and organs of the body. This approach offers an economical advantage in that fewer animals are required for residue studies.In domestic animals, as in humans, the disposition of most drugs can be interpreted in terms of a 2- (generally) or 3-compartment open model. Species variations in pharmacokinetic behaviour of a drug are usually attributed to differences in the rate of elimination rather than distribution and metabolism of the drug, although the principal metabolic pathway may differ. With certain notable exceptions, the herbivorous species (horses and ruminant animals) metabolise lipid-soluble drugs more rapidly than carnivorous species (dogs and cats). Humans metabolise drugs slowly in comparison with animals. Half-life values reflect this; insufficient data are available to base interspecies comparison on mean residence time. Intrinsic hepatic clearance of phenazone (antipyrine) [microsomal oxidation] in humans is approximately one-seventh of that in domestic animals. The physiological basis of species variations in the t½values of drugs eliminated by a combination of biotransformation and excretion processes could be ascribed to differences in the rates of metabolic pathways and the influence of urinary pH on the extent of renal tubular reabsorption of unchanged drug. In any species, urinary pH is dependent mainly on dietary habit. For drugs eliminated entirely by renal excretion, allometric scaling of data obtained in animals can be used to predict pharmacokinetic parameters describing disposition in humans.Certain physiological states, prolonged (>48h) fasting, some disease conditions or pharmacokinetic drug interactions may alter the disposition of drugs in animals. The age-related development of hepatic microsomal associated drug metabolic pathways and renal excretion mechanisms also varies among species. In calves, lambs, kids, piglets and puppies these metabolic pathways develop rapidly during the first 3 to 4 weeks after birth. At 8 to 12 weeks they approach activity similar to that in adult animals. Renal function appears to mature within the first 1 to 2 weeks after birth in foals, calves, lambs, kids and piglets, while it takes longer (4 to 6 weeks) to mature in puppies. The rate of development of the major drug elimination processes in newborn animals is species-dependent.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, which appeared in the previous issue of the Journal, the applications of pharmacokinetics in PET were discussed in order to derive quantitative measures of physiological function. Part II examines the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

Cefotaxime is a third generation cephalosporin antimicrobial agent which has received wide acceptance as a first-line antibiotic for many infections in neonates, infants and children. With an average elimination half-life of about 1h, cefotaxime is not considered to be a ‘long half-life cephalosporin’ like ceftriaxone. For this reason, currently accepted dosage regimens for cefotaxime in infants and children employ a dosage of 50 mg/kg every 6h.Re-examination of the paediatric pharmacokinetic data for cefotaxime and use of simple multiple-dose pharmacokinetic simulation of alternative dosage regimens was performed. From this analysis, regimens administering 75 mg/kg of the drug every 8h or every 12h were projected to produce serum cefotaxime concentrations adequate to effectively kill many of the common pathogens against which the drug is currently indicated for use in children. The clinical utility of these alternative dosage regimens was supported by a review of the medical literature and examination of the clinical results from studies in neonates, infants and children where cefotaxime was administered in 2 to 3 divided doses daily. It would appear, therefore, that increasing the cefotaxime dosage to 75 mg/kg administered at 8h intervals would result in less frequent drug administration which would not be expected to compromise safety and efficacy. Alternative dosage regimens for cefotaxime merit further consideration and clinical evaluation before they become commonly used in paediatric therapeutics.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

The pharmacokinetics of vancomycin were studied in continuous ambulatory peritoneal dialysis patients with peritonitis. Six patients received an intraperitoneal loading dose of 15 mg/kg and 4 received an intraperitoneal dose of 25 mg/L. The ability of 2 methods to predict serum concentrations during the loading dose exchange was determined. The mean serum concentration after the exchange was 17.8 ± 2.2 mg/L in patients receiving the loading dose. The mean dialysis clearance in all patients was 0.94 ± 0.34 L/h. 66.6 ± 13.4% of a dose was absorbed into the circulation in 4h. The volume of distribution was 0.61 ± 0.46 L/kg, and the half-life for equilibration of vancomycin into the circulation from dialysate was 2.76 ± 0.94h. Two methods of predicting serum vancomycin concentrations were tested, with 1 method predicting values significantly different from measured concentrations while the other did not. Serum vancomycin concentrations can be accurately predicted during a loading dose exchange.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS

摘要:

To investigate the influence of the presence of oedema on the pharmacokinetics and pharmacodynamics of furosemide (frusemide) we selected 9 hospitalised patients (mean age 70.3 years, range 59 to 84 years) with severe congestive heart failure (NYHA III to IV) and an assessed amount of peripheral oedema of at least 5kg. In these patients the absorption of a single oral dose of furosemide 250mg was studied when their heart failure was decompensated and again, after intensive therapy, when it was clinically compensated. The mean (± SEM) weight loss after clinical treatment was 12.0 ± 2.2kg. Individual furosemide plasma concentration-time curves could be fitted adequately to a 1-compartment model with 1 first-order absorption and elimination process, in which absorption took place in 2 parts with different lag times. Comparing the decompensated state with the compensated state we did not find significant differences in pharmacodynamics, absorption half-life, elimination half-life, time to peak serum concentration, peak serum concentration itself and area under the plasma concentration-time curve. However, the relative amount of furosemide absorbed in the first fraction was significantly increased after compensation. We conclude that the presence of massive oedema in patients with congestive heart failure has a minor influence on the pharmacokinetics and pharmacodynamics of high dose oral furosemide.

ISSN:0312-5963    

出版商:ADIS    

年代:1992

数据来源: ADIS