Clinical Relevance of Pharmacokinetics

Tognoni, Gianni; Bellantuono, Cesario; Bonati, Maurizio; D’Incalci, Maurizio; Gerna, M.; Latini, Roberto; Mandelli, M.; Porro, Maria Grazia; Riva, Emma

doi:10.2165/00003088-198005020-00001

Cited by 13 publications

(2 citation statements)

References 212 publications

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“…This article has arisen from a series of joint research programmes of a group of clinicians working in general and highly specialised intensive care units, and a group of clinical pharmacologists interested in the assessment of what in their discipline really does matter in clinical practice (Bonati & Tognoni 1984;Farina et al 1981;Tognoni et al 1980).…”

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Clinical Pharmacological and Therapeutic Considerations in General Intensive Care

Farina

Bonati

Iapichino

et al. 1987

Drugs

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The application of clinical pharmacological concepts and therapeutic standards in intensive care settings presents particularly difficult problems due to the lack of adequately controlled background information and the highly variable and rapidly evolving clinical conditions where drugs must be administered and their impact evaluated. In this review, an attempt has been made to discuss the available knowledge within the framework of a problem-oriented approach, which appears to provide a more clinically useful insight than a drug-centred review. Following a brief discussion of the scanty data and the most interesting models to which reference can be made from a pharmacokinetic point of view (the burn patient being taken as an example), the review concentrates on the main general intervention strategies in intensive care patients. These are based mainly on non-pharmacological measures (correction of fluid and electrolyte balance, total parenteral nutrition, enteral nutrition, oxygenation and ventilatory management) and are discussed with respect to the specific challenge they present in various clinical conditions and organ failure situations. In addition, 4 major selected clinical conditions where general management criteria and careful use of prophylactic and therapeutic drug treatments must interact to cope with the variety of presentations and problems are reviewed. These include: acute cerebral damage; anti-infective prophylaxis and therapy; cardiovascular emergencies; and problems of haemostasis. Each problem is analysed in such a way as to frame the pharmacological intervention in its broader context of the underlying (established or hypothesised) pathophysiology, with special attention being paid to those methodological issues which allow an appreciation of the degree of reliability of the data and the recommendations which appear to be practiced (often haphazardly) in intensive care units. The thorough review of the published literature provided (up to mid-1986) clearly shows that in this field the quality of randomised controlled and epidemiological studies is rather unsatisfactory. It would be highly beneficial to research and to clinical care if larger multicentric protocols and prospective epidemiological comparative investigations could be carried out to investigate more timely and adequately the variables which determine drug action, and the final outcome in the many subgroups of patients which must be considered in a proper stratification of intensive care unit populations.

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Clinical Pharmacological and Therapeutic Considerations in General Intensive Care

Farina

Bonati

Iapichino

et al. 1987

Drugs

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“…Only limited information, however, on the pharmacokinetics of antibiotics in patients or experimental animals with septicemia is available (2,13). It might be anticipated that during such a severe pathological condition, the altered blood flow and permeability of blood vessel walls would influence the pharmacokinetics of antibiotics.…”

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Pharmacokinetics of cephalosporins in normal and septicemic rabbits

Ganzinger¹,

Haslberger²

1985

Antimicrob Agents Chemother

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The differences in the pharmacokinetics of cefotaxime, moxalactam, and CPW 86-363, a new expandedspectrum cephalosporin, were studied in healthy rabbits and in rabbits infected intravenously with Streptococcus pneumoniae. The pharmacokinetic analysis of concentration-time courses in the sera of infected animals according to a two compartment-model evidenced a clear decrease of drug fractions in the central compartment but enhanced drug fractions in the peripheral compartment. The shift was more pronounced in animals which received CPW 86-363 (60%; P < 0.05) than in those which received cefotaxime (20%) or moxalactam (5%). Corresponding increases in drug concentration were observed in soft tissue interstitial fluid; therefore, the areas under the curve and mean residence times in the soft tissue interstitial fluid of infected rabbits were prolonged. The shift of drug fractions from the central compartment to other body fluid compartments during infection was thought to be due to cardiovascular changes associated with fever. No changes in serum binding of the three drugs were found during the course of the infection. The quantitative differences in the extent of altered distribution properties of the drugs might be due to variations in the physicochemical properties of the drugs.The pharmacokinetics of various antibiotics have been extensively studied in healthy individuals and in patients with various degrees of renal or hepatic impairment. Only limited information, however, on the pharmacokinetics of antibiotics in patients or experimental animals with septicemia is available (2, 13). It might be anticipated that during such a severe pathological condition, the altered blood flow and permeability of blood vessel walls would influence the pharmacokinetics of antibiotics. Recent results indicate that during experimental meningitis in rabbits, the volume of distribution is larger than that in healthy rabbits (10). Hence, the concentrations of cefoperazone, moxalactam, and cefotaxime in the sera of infected rabbits are lower than those in the sera of healthy rabbits. We therefore studied the influence of septicemia on the pharmacokinetics of three expanded-spectrum cephalosporins, cefotaxime, moxalactam, and CPW 86-363, by monitoring their concentrations in serum and in the fluid of subcutaneously implanted diffusion chambers. MATERIALS AND METHODSIn each set of experiments, one group of four healthy and one group of four infected male chinchilla rabbits (weight, 3.0 to 3.5 kg each) were used. were obtained from a marginal ear vein of each rabbit before and at 5, 15, and 30 min and 1, 2, 3, and 4 h after drug administration. In addition, viable bacteria were estimated from blood samples drawn at 1, 2, 5, 6, 8, and 15 h after the inoculation and at the same time as blood was sampled for pharmacokinetic analysis.In each rabbit, six diffusion chambers filled with physiological saline were implanted subcutaneously in the back 3 days before the study, by the procedure of Laber et al. (8). These chambers consist of filter...

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Elementary Pharmacokinetics and Pharmacodynamics

Maxwell

1984

Principles of Paediatric Pharmacology

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Clinical Relevance of Pharmacokinetics

Cited by 13 publications

References 212 publications

Clinical Pharmacological and Therapeutic Considerations in General Intensive Care

Clinical Pharmacological and Therapeutic Considerations in General Intensive Care

Pharmacokinetics of cephalosporins in normal and septicemic rabbits

Elementary Pharmacokinetics and Pharmacodynamics

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