Pharmacokinetic case for giving 6-mercaptopurine maintenance doses at night.
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Child↗
Biomedical subjects
S J Soldin
Publications and source records attributed to S J Soldin.
Volume of distribution of phenytoin not altered in storage disease.
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Adolescent↗
Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer.
The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (+/- SD) of 46.2 +/- 20.2 min during the first course and 37.8 +/- 18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (+/- SD) of 57.8 +/- 19.3 h during the first course and 86.6 +/- 33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61 +/- 0.32 l/h/m2 and 0.45 +/- 0.16 l/h/m2 for the first and the second course, respectively. We conclude that: urinary platinum excretion is variable between patients and with time; a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and the body's elimination pathways clear less platinum upon repeat administration.
Adult↗
Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers.
Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml X min-1 X 1.73 m-2. Peak plasma concentrations of 10-20 ng X ml-1 were obtained 1-3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
Absorption↗
Effect of salbutamol on resting energy expenditure in patients with cystic fibrosis.
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Administration, Inhalation↗
Receptor radioligand system for measuring digoxin activity.
The purpose of this study was to develop and evaluate a receptor radioligand assay (RRA) for the measurement of digoxin, its metabolites, and endoxin and to compare the results of this assay with those of a fluorescence polarization immunoassay (FPIA) for digoxin. The within-run coefficients of variations for the RRA at digoxin concentrations of 2.0 and 5.0 nmol/L were 21 and 10%, respectively. Serum samples collected from 33 volunteers (not on digoxin medication) measured in the RRA resulted in levels less than 1.23 nmol/L digoxin equivalents (1.23 nmol/L is the lower level of sensitivity for this system). Serum samples collected from 29 patients receiving digoxin for therapeutic purposes and measured in the RRA gave a mean of 3.39 nmol/L digoxin equivalents. The samples collected from the patients receiving digoxin were also measured using FPIA with a mean of 1.75 nmol/L digoxin. The interference of progesterone, 11-alpha-hydroxyprogesterone, cortisone, and six digoxin metabolites on the binding of 3H-ouabain in the RRA was also evaluated.
Animals↗
Analysis of phosphoramide mustard by reversed-phase ion pair high pressure liquid chromatography.
The analysis of phosphoramide mustard by reversed-phase ion pair high pressure liquid chromatography using ultraviolet detection is described. The method will enable measurement of serum concentrations of phosphoramide mustard over a period of approximately 24 h after an i.v. dose of 60 mg/kg of cyclophosphamide and requires 0.5 ml of serum or plasma. The between-day precision of the assay at concentrations of 0.34, 2.76, and 6.90 mg/L gave coefficients of variation of 16, 10, and 9%, respectively. The percentage analytical recovery of phosphoramide mustard is 35%. Preliminary results providing pharmacokinetic data on two adults undergoing high-dose cyclophosphamide treatment prior to bone marrow transplant are presented.
Chromatography, High Pressure Liquid↗
Cardiac glycosides.
Despite continuous controversy associated with a variety of aspects of the pharmacology of the cardiac glycosides, it appears that these agents will continue to be widely used in the future. Current methods for the measurement of digoxin are unreliable and allow measurement of both cardioinactive metabolites of digoxin and endogenous digoxin-like substances. As a result, the therapeutic monitoring of digoxin concentrations should, for the most part, be limited to an assessment of patient compliance and confirmation of a clinical impression of drug toxicity.
Animals↗
Palatability and relative bioavailability of an extemporaneous carbamazepine oral suspension.
The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspensions was tested, and the bioavailability of the unflavored suspension relative to that of the tablet used in its manufacture was determined in a randomized, crossover study of 12 healthy volunteers. Carbamazepine 400 mg was administered with a glass of water as either 20 mL of unflavored oral suspension (20 mg/mL) or two 200-mg tablets. Subjects were randomly assigned to receive first either the tablets or the suspension in crossover fashion on two days separated by at least two weeks. Blood samples were taken just before and at various times up to 72 hours after the carbamazepine dose. Serum samples were assayed for carbamazepine content by high-performance liquid chromatography. Of five flavored and unflavored carbamazepine suspensions tested in eight volunteers, the cherry-mint formulation was the least palatable. There was no trend in preference among the remaining suspensions (banana, tutti-frutti, grape, and unflavored). Mean values of maximum serum concentration and absorption rate constant were significantly greater for the unflavored suspension (5.7 mg/L [24 mumol/L] and 0.832 hr-1, respectively) than for the tablet (4.9 mg/L [20.8 mumol/L] and 0.266 hr-1, respectively). The mean time to maximum concentration was significantly shorter after suspension administration (3.87 hours) than after tablet administration (11.8 hours). There was no significant difference in the extent of absorption of the tablet and suspension formulation as reflected by the corrected values of the area under the serum concentration-versus-time curves. The mean (+/- S.D.) bioavailability of the suspension relative to the tablet was 94.46% +/- 20.42 (range 76.35-132.72%).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Pharmacokinetics of cimetidine after subchronic administration.
The influence of cimetidine on its own pharmacokinetics after subchronic administration was assessed in 8 healthy volunteers, aged 26-29 years. On control Day 1, each subject received cimetidine 300 mg i.v., and serum and urine samples were obtained. Each subject was initiated on cimetidine 600 mg b.i.d. orally for 2 weeks. There were 3 further study days repeated after 1 and 2 weeks of cimetidine dosing and 1 week after stopping cimetidine. There was no significant difference in the mean total body clearance of cimetidine among the 4 study days. Mean elimination t1/2 beta and V beta were similarly unchanged. However mean renal clearance (CLR) and fe were significantly increased following 2 weeks of drug dosing (CLR 5.41 ml X min-1 X kg-1; fe 0.61) compared to control (CLR 4.00 ml X min-1 X kg-1; fe 0.48). Although the non renal clearance was reduced from control values of 4.29 to 3.51 ml X min-1 X kg-1 following 2 weeks of dosing the difference was not significant. Dosage adjustment of cimetidine appears unnecessary after short-term dosing in the presence of normal renal function.
Administration, Oral↗
A study of lipid effects on the digoxin immunoassay and on the binding to and activity of Na+/K+-ATPase.
The present study has examined the cross-reactivity of fatty acids and mono- and di-glycerides in the fluorescence polarization immunoassay for digoxin. The ability of these compounds to inhibit 86Rb uptake by the erythrocyte as well as their ability to displace 3H-ouabain from membrane-bound dog kidney ATP-ase was also assessed. Some unsaturated fatty acids (palmitoleic, palmitelaidic, oleic, linoleic, linolelaidic, linolenic, gamma-linolenic and arachidonic) were found to cross-react significantly in the digoxin immunoassay and to inhibit 3H-ouabain binding to membrane-bound Na+/K+-ATPase. Of the monoglycerides studied mono-11-eicosenoin was found to cross-react in the digoxin immunoassay, inhibit red cell 86Rb uptake and displace 3H-ouabain from its receptor, membrane-bound Na+/K+-ATPase. Two other monoglycerides, 1-monolinoleoyl and 1-monolinolenoyl glycerides, were able to displace 3H-ouabain from membrane-bound Na+/K+-ATPase, but had no effect on the digoxin immunoassay or on red cell 86Rb uptake.
Animals↗
Determinants of drug disposition in man.
This article reviews some of the important determinants of variation in drug disposition such as age, gender, body weight, diet, environmental influences, drug - protein interactions, compliance, drug - drug interactions, endogenous substances, disease states, circadian variation and genetics.
Adult↗
Clinical evaluation of a dry chemistry strip theophylline assay.
In this dry chemistry strip immunoassay, flavin adenine dinucleotide (FAD) conjugated theophylline competes with theophylline in the sample for binding to a specific monoclonal antibody. Unbound conjugate can then activate apoglucose oxidase, the activity of which is coupled to a peroxidase chromogenic reaction that allows kinetic monitoring by reflectance photometry. Thirty microliters of diluted sample is placed onto the reagent pad. The strip is inserted into the analyzer, and a digital readout appears 80 s later. Within-run precision was 4.5% based on patient duplicates. Between-day precision was 7.6% at 10 mg/L (n = 29) and 4.5% at 20 mg/L (n = 27). The assay was linear to at least 35 mg/L. There was good agreement between the test method and fluorescence polarization immunoassay: y (test) = -0.2865 + 1.085x (reference), n = 79, r = 0.980, Syx = 1.64. The assay showed good specificity except in patients receiving dimenhydrinate or suffering from renal failure. This system of assay provides reliable measurement of theophylline and will allow easy accessibility to this measurement for physicians working in emergency departments or private offices.
Adult↗
Digoxin--issues and controversies.
This review deals briefly with the clinical pharmacology of digoxin and reviews in some depth the problems inherent in methods of digoxin measurement. Digoxin-like factors (materials that cross react in digoxin immunoassays) are discussed, and some current evidence suggesting the existence of a new hormone, endoxin (endogenous digoxin), is summarized.
Administration, Oral↗
Further problems with digoxin measurement.
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Benzenesulfonates↗
Control of gastric pH with cimetidine: boluses versus primed infusions.
Previous studies suggest that antacids are more effective than intravenous cimetidine in maintaining the gastric pH above 4.0 in acutely ill patients. We hypothesized that this was because blood levels of cimetidine are not sustained at therapeutic levels with the bolus doses. The purpose of this study was to compare gastric pH and serum cimetidine levels when cimetidine was administered as bolus versus infusion. We studied 23 acutely ill patients who received intravenous cimetidine given as boluses and primed infusions. The gastric pH could be maintained above 4.0 with infusions of up to 50 mg/h (1200 mg/day) in 20 patients, compared with only 5 patients with bolus administrations of up to 300 mg every 6 h (1200 mg/day). The differences in ability to maintain the gastric pH above 4.0 were entirely due to the reduced ability of bolus infusion to maintain an adequate serum level. Neither technique could maintain the pH above 4.0 in 3 patients, all of whom had received cimetidine recently. A gastric pH greater than 4.0 correlated directly with a therapeutic serum cimetidine level. We conclude that infusions of cimetidine are better able to sustain therapeutic blood levels and, therefore, are superior to bolus cimetidine in maintaining gastric pH above 4.0. Some patients, however, may not respond to cimetidine even if therapeutic levels are achieved and may require supplemental antacids.
Adult↗
Digoxin immunoreactivity in cord and maternal serum and placental extracts. Partial characterization of immunoreactive substances by high-performance liquid chromatography and inhibition of Na+, K+-ATPase.
Digoxin-like immunoreactive substances (DLIS) have been successfully extracted and concentrated from cord serum, mixed (cord and maternal) serum and placentas. Similar substances have also been extracted from normal adult serum, but DLIS in this medium are present in much lower concentrations. Concentrated DLIS have been separated into several immunoreactive fractions by use of reverse-phase high-performance liquid chromatography. Immunoreactive fractions were tested for their ability to inhibit the Na+,K+-ATPase by measuring the 86Rb-uptake of red blood cells in the presence of these fractions. A potent inhibitor was identified in an immunoreactive fraction which also contains progesterone, but the results suggest that the pump inhibitor is not progesterone. Cross-reactivity studies utilising fluorescence polarization immunoassay have shown that cortisone is the most potent immunoreactive substance of cord serum.
Chromatography, High Pressure Liquid↗
Organization and efficacy of a therapeutic drug monitoring consultation service in a pediatric hospital.
On July 1, 1982, a therapeutic drug monitoring (TDM) consultation service was instituted in the hope of improving the decision-making of clinicians with respect to drug therapy. Thirteen different drugs are monitored daily, with an average load of 1,600 inpatient samples per month. The team consists of clinical pharmacology fellows and staff who are available 7 days a week to monitor all drug levels that are outside the putative therapeutic range. In order to evaluate the efficacy of this service in preventing development of potentially toxic drug concentrations, the TDM data from July 1982 to December 1983 have been reviewed. The percentage of toxic levels from the total sample load was significantly lower in the period of July-December 1983 compared with July-December 1982 at the beginning of the service (2.25% vs. 4.25%, p less than 0.01). Since January 1983, the percentage has been maintained at less than 3%. A TDM consultation service can help to optimize the use of drug monitoring data by physicians and may lead to improved prescribing in a hospital setting.
Adolescent↗