Plasma concentration-time data resulting from constant rate intravenous infusion may be analysed in two ways: Samples may be collected both during and after infusion and fit to an infusion model. Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus. The purpose of this study was to contrast these two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration-time data were computer-generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area-dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady-state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration-time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rate constants.

Humans↗

PubMedDate not supplied

The influence of sucralfate on ibuprofen absorption in healthy adult males.

Sucralfate (Carafate) is a new anti-ulcer agent the effects of which are mediated locally in the gastrointestinal tract. The use of this compound in conjunction with ulcerogenic drugs such as ibuprofen may represent a means of reducing gastrointestinal irritation. Combined oral therapy, however, requires evaluation of a potential interaction in absorption between those agents. The purpose of this study was to examine the influence of sucralfate coingestion on ibuprofen absorption. Twelve normal, healthy male subjects ingested a single oral 400 mg dose of ibuprofen alone or with sucralfate given as 1 g doses four times a day for 2 days prior to and during the study. Ibuprofen serum concentrations were measured for 12 hours following dosing. Parameters associated with rate of absorption (i.e. Cmax, tmax, Ka) were significantly altered in the presence of sucralfate (p less than 0.05). In contrast, the relative bioavailability of ibuprofen was not significantly different between treatments (p greater than 0.05). Therefore, sucralfate does not alter the extent of ibuprofen absorption and would not be expected to change the response to that anti-inflammatory agent.

Administration, Oral↗

PubMedDate not supplied

Cimetidine disposition in patients undergoing continuous ambulatory peritoneal dialysis.

Cimetidine disposition was determined in six patients undergoing continuous ambulatory peritoneal dialysis to ascertain the need for modification of conventional dosing regimens. Blood, dialysis fluid, and urine were collected for 48 hours after administration of a single intravenous dose of cimetidine. The following values were obtained: elimination half-life, 4.3 hours; systemic or total body clearance, 191 +/- 55 ml/min; and dialysis clearance, 4.2 +/- 3.1 ml/min. Approximately 2% of a cimetidine dose is removed by dialysis, indicating that there is no need to adjust the conventional renal failure dosing regimen in patients undergoing continuous ambulatory peritoneal dialysis.

Aged↗

PubMedDate not supplied

Separation and quantitation of the enantiomers of methamphetamine and its metabolites in urine by HPLC: precolumn derivatization and fluorescence detection.

To study the disposition kinetics of methamphetamine (MAP), we have developed a sensitive high-performance liquid chromatographic (HPLC) assay to quantitate the enantiomers of MAP and its major metabolites, amphetamine (AP), p-hydroxymethamphetamine (p-OH-MAP), and p-hydroxyamphetamine (p-OH-AP), the latter two of which are hydroxylated metabolites, in rat urine. To determine conjugated hydroxylated metabolites, urine samples were treated with beta-glucuronidase. Both hydrolyzed and nonhydrolyzed p-OH-MAP and p-OH-AP were extracted into ethyl acetate and back extracted with 0.05M HCl. To determine MAP and AP, urine samples were extracted with benzene, followed by back extraction into 0.05M HCl. The acid layer was collected, and to it was added (-)-1-(9-fluorenyl)ethyl chloroformate (FLEC) for the derivatization of MAP and its metabolites. Derivatization was allowed to proceed for 24 h at room temperature. The derivatized products were separated on a C18 column with a mobile phase consisting of acetate buffer (pH 3.6)-acetonitrile-tetrahydrofuran. Quantitation was achieved using a fluorescence detector at an excitation wavelength of 265 nm and an emission wavelength of 330 nm. Linear standard curves were obtained over the concentration range of 5-100 ng/mL. The interday and intraday coefficients of variation for the assay for all eight enantiomers at 10 and 75 ng/mL were less than 13%. The detection limit was 5 ng/mL or 0.5 ng on-column.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Enantiomeric determination of amphetamine and methamphetamine in urine by precolumn derivatization with Marfey's reagent and HPLC.

An analytical method was developed for enantiomeric determination of amphetamine and methamphetamine in human urine. The enantiomers were isolated from urine by solid-phase extraction, and diastereomers were formed by derivatization with the chiral Marfey's reagent (1-fluoro-2,4-dinitrophenyl-5-l-aniline amide). The diastereomers were separated by reversed-phase high-performance liquid chromatography in a water/methanol mobile phase and detected by absorbance spectrophotometry at 340 nm. Linear standard curves were obtained for all four enantiomers over a concentration range of 0.16-1.00 mg/L in urine. The detection limit was 0.16 mg/L urine for each enantiomer, and the limit of quantitation was 0.40 mg/L. The urine of 10 decedents was analyzed by this method and by a previously published precolumn derivatization procedure using (-)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as the derivatizing agent and fluorescence detection. Comparison of the results of the two methods by linear regression showed comparable results for both d-amphetamine and d-methamphetamine. Neither method detected the presence of the l-enantiomers in the urine samples.

Alanine↗

PubMedDate not supplied

Quantitative analysis of phencyclidine and metabolites by capillary column gas chromatography.

A sensitive capillary gas chromatography (GC) procedure was developed for the analysis of phencyclidine (PCP), two of its monohydroxy-metabolites, and a recently identified pentanoic acid metabolite. Two separate, but sequential, integrated extraction techniques were necessary to isolate all of the compounds from a 1.0-mL biological sample. Two GC techniques were necessary to analyze all the compounds; both methods used a capillary column and a nitrogen phosphorus detector (NPD). The first procedure permitted isolation and quantitation of PCP and two monohydroxy-metabolites. A second extraction of the biological samples permitted measurement of the pentanoic acid metabolite. The analytical methods illustrate good reproducibility based on within-day and day-to-day variation. Serum and urine samples were analyzed from a dog administered PCP to illustrate the utility of this procedure.

Animals↗

PubMedDate not supplied

Clinical pharmacokinetics of digitoxin.

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Administration, Oral↗

PubMedDate not supplied

Pharmacokinetics tricks and traps: drug dosage adjustment in renal failure.

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Creatinine↗