Clinical pharmacokinetics during continuous haemofiltration.

Continuous haemofiltration is an extracorporeal technique that is increasingly used to remove fluid, electrolytes, and other waste products from the blood supply of critically ill patients with acute renal failure. Continuous arteriovenous haemofiltration (CAVH), where the blood exits the body from an artery and re-enters through a vein, is widely used. Continuous venovenous haemofiltration (CVVH), where blood both exits and enters through a vein by way of a mechanical pump, avoids problems that result from the variable ultrafiltration rate found during CAVH. Continuous arteriovenous or venovenous haemodiafiltration (CAVHD or CVVHD) combine continuous haemofiltration and haemodialysis. All methods involve ultrafiltration of the patient's blood through a filter that is highly permeable to water and small molecules. Drug elimination by haemofiltration depends mainly on the rate of ultrafiltration, the drug protein binding and the sieving coefficient of the membrane. Because patients undergoing continuous haemofiltration have impaired renal function, dosage reduction is often recommended so that adverse drug reactions are avoided. In contrast, if drug removal by haemofiltration is significant, dosage supplementation may be required to ensure therapeutic efficacy of the drug. Therefore, knowledge of the impact of continuous haemofiltration on drug elimination and the pharmacokinetic profile of drugs is essential to good clinical management. The currently available information on the clinical pharmacokinetic aspects of drug therapy during continuous haemofiltration are summarised. Drugs commonly associated with haemofiltration therapy are tabulated with updated pharmacokinetics and drug-monitoring information.

Formation of biogenic amines by isolated kidneys of spontaneously hypertensive rats.

Kidneys form dopamine (DA) from L-dopa and serotonin from L-5-hydroxytryptophan (L-5-HTP) via aromatic L-amino acid decarboxylase. We compared the ability of isolated perfused kidneys from adult (20-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) to form these biogenic amines. Renal vascular resistance (RVR) was greater in perfused kidneys from SHR (n = 10) than WKY (n = 8) (p less than 0.01). Slight decreases in RVR were observed during L-dopa infusion but these were unrelated to DA formation. L-Dopa infusion was associated with greater DA output in SHR than WKY in both the renal venous and urinary effluents although the latter did not achieve statistical significance. L-5-HTP increased RVR to a greater degree in SHR than WKY kidneys. This was associated with larger quantities of serotonin in the urinary and venous effluents and greater pressor responses to exogenous serotonin in SHR than WKY kidneys; however, either parameter alone was not significantly increased. Our findings do not support a deficiency of intrarenal DA formation as a pathogenic factor for hypertension in SHR. Biogenic amine formation is as great if not greater in SHR than WKY kidneys and appears to contribute largely to the greater increases in renal resistance seen in SHR kidneys on infusion of L-5-HTP. Enhanced renal serotonin formation may elevate blood pressure, whereas enhanced renal DA formation would favor blood pressure lowering, perhaps as a compensatory mechanism.

A Weibull distribution model for intradermal administration of ceftazidime.

The pharmacokinetics of 1 g of ceftazidime administered intradermally was studied in seven healthy volunteers. The objective of the present study was to find the most appropriate mathematical model to describe the drug intake process. The concentration of ceftazidime in plasma was measured by HPLC. The disposition of the drug was described by a one-compartment pharmacokinetic model, with drug intake occurring by different processes: a zero-order process due to the administration and a first-order intake from the injection site to the systemic circulation. The Weibull model was considered as an approximation of the overall process. The mean Weibull parameters were td (time necessary to transfer 63% of the administered drug into the systemic circulation) of 2.75 +/- 0.75 h, and f (shape) of 1.04 +/- 0.15. The mean elimination half-life was 2.0 +/- 0.4 h. The area under the concentration versus time curve obtained in this study (139 +/- 46 mg.h/L) is very near to literature values reported after single intravenous doses of 1 g of ceftazidime, suggesting that the bioavailability of ceftazidime after intradermal administration may be approximately 100%. Moreover, the mean peak plasma concentration (37 +/- 16 mg/L) is in the same range as that reported in the literature after intramuscular administration of a single dose of 1 g.

Renal functional status and patterns of catecholamine excretion.

Twenty-four hour urinary catecholamine measurements were obtained in seven normal individuals and 23 patients with essential hypertension or renal disease. As renal function decreased, large reductions in the excretion of free catecholamines and total dopamine were measured. Since urinary catecholamine measurements are used for diagnostic and physiologic studies, our data indicate a need to assess renal function for accurate interpretation of these measurements. Our results are also consistent with a renal origin for a major portion of the urinary dopamine content.

MacCueSee: a quality control program for the Macintosh computer.

MacCueSee was written to perform routine calculations on quality control concentration values from radioimmunoassay. It is written in Microsoft QuickBASIC for the Apple Macintosh computer. The program calculates within and between assay standard deviation (S.D.) and coefficient of variation from a spreadsheet file containing concentration values of controls analyzed. It also calculates the average concentration +/- 1 S.D. and contraction +/- 2 S.D. to establish between assay ranges. Its flexibility permits varying replicates between assays and automatic exclusion of missed assays. Within assay variability calculations are made for single, duplicate, and triplicate tubes. Results are displayed and can optionally be printed. In addition to radioimmunoassay, MacCueSee can be applied to a number of analytical methods in which quality control is monitored. An example of program use is included.

Dopamine and L-dopa potentiation of pressor responses to norepinephrine in isolated perfused rat kidneys.

The ability of l-dopa and dopamine to modulate renal vascular responses to norepinephrine (NE, 50-150 ng) was examined in isolated Tyrode-perfused kidneys from male Sprague-Dawley rats. Renal pressor responses to bolus injections of NE were constant during saline infusion. In contrast, l-dopa (15 micrograms/min and 75 micrograms/min) and dopamine (15 micrograms/min) infusions that did not alter baseline perfusion pressure increased pressor responses to NE significantly. Concomitant infusion of the aromatic l-amino-acid decarboxylase inhibitor carbidopa (20 micrograms/min) suppressed the ability of l-dopa (75 micrograms/min) but not dopamine to enhance renal pressor responses to NE. The pressor potentiation of NE did not appear to be the result of a general musculotropic effect or altered alpha-1 adrenoreceptor activity since increased vasoconstrictor responses to phenylephrine (PE) and serotonin (5-HT) were not observed. Infusions of cocaine (15 micrograms/min) enhanced the renal pressor effects of NE but not PE in similar fashion to l-dopa and dopamine. In the presence of cocaine, l-dopa did not potentiate NE constriction further. These results suggest that endogenous or exogenous dopamine in the kidney may affect neuronal NE uptake to enhance its renal vascular effects.