Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous furosemide.

Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using the dog as a model animal. Each of six dogs received 8-hr constant intravenous infusion of 20 mg (15 mg used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II), and 100% replacement (treatment III) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (treatment IV). Most pharmacokinetic parameters, such as plasma clearance, steady-state volume of distribution, mean residence time, and terminal half-life, were essentially the same in all four treatments.

A new simple approach to study the effect of changes in urine flow and/or urine pH on renal clearance and its applications.

After entering the renal tubular lumen either through glomerular filtration or tubular secretion, drug molecules are considered to be removed from there by two competing processes: tubular fluid flow for urinary excretion and tubular reabsorption into blood circulation. The relative overall magnitude of the "force" or "efficiency" of these two processes will determine the fraction of drug molecules to be either excreted or reabsorbed, and hence their renal clearance (CLr). Urine flow rate (Q) is assumed to be proportional to the mean flow rate of tubular fluid at reabsorption sites (mainly in distal tubules), and used as an index to indirectly estimate the relative reabsorption "force" or "efficiency" (this may also be called apparent intrinsic reabsorption clearance).

Absorption of iothalamate after oral administration and absorption enhancement by amino acids in dogs and rats.

The oral absorption of iothalamate and the effect of amino acids on its absorption were studied in 6 dogs and 6 rats using a simple HPLC assay. The results showed that iothalamate was absorbed in dogs, averaging 9.9, 8.

Renal and non-renal clearances of iothalamate.

An evaluation of the literature indicated that certain aspects of the disposition kinetics of iothalamate, important to the accurate determination of glomerular filtration rate in dogs and humans, remain to be resolved. The simultaneous clearances of iothalamate and inulin in 5 dogs were determined at three steady-state iothalamate plasma levels (2, 10, and 40 micrograms ml-1) following various rates of intravenous infusion. The iothalamate clearances, both renal and non-renal, were concentration-independent.

Rapid estimation of total body clearance of theophylline in patients receiving intravenous aminophylline infusion.

The method of Chiou to rapidly estimate theophylline total body clearance using two serum concentration data during the early stage of intravenous aminophylline infusion was evaluated in 16 patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. The observed serum concentrations at later times were compared with those predicted. The mean prediction error for serum concentrations was 4.

Urinary pH and urine flow independent renal clearance of methotrexate in dogs.

The effects of urine flow and pH on methotrexate renal clearance were studied in seven conditioned male Beagle-Mongrel dogs. Steady-state plasma methotrexate and inulin concentrations were achieved by i.v.

Clearance studies of methotrexate in dogs after multiple-rate infusion.

Plasma, renal, and nonrenal clearances of methotrexate as well as their interrelationship were studied in five conditioned male beagle-mongrel dogs using the multiple-rate infusion method. Steady-state plasma methotrexate concentrations of 1, 20, and 100 micrograms/ml were targeted for by i.v.

Concentration and pH dependent steady-state volume of distribution of methotrexate estimated by a simple physiologically based method.

The effects of plasma concentration and pH on the steady-state volume of distribution, Vss, of methotrexate (MTX) were studied in five conditioned male beagle-mongrel dogs. Steady-state plasma MTX concentrations of approximately 1, 20, and 100 micrograms/ml were targeted for by i.v.

A new model-independent physiological approach to study hepatic drug clearance and its applications.

After entering the liver a drug molecule is removed by two competitive processes: (a) blood flow to carry it away intact from liver and (b) elimination by hepatic enzyme(s). The relative magnitude of the overall force or efficiency of these two processes will statistically decide its probability for elimination, i.e.

Pharmacokinetics in blood IV: unusual distribution, storage effect and metabolism of methotrexate.

The whole blood from three human subjects, one dog and four rabbits was spiked with methotrexate (MTX) to yield appropriate concentrations, and was incubated at 37 degrees C and 50 oscillations per min. MTX was found to exhibit unusual distribution kinetics in whole blood; plasma MTX concentrations generally dropped to a minimum at about 5 min then increased and fluctuated somewhat irregularly afterwards. Differences of up to 21, 19 and 32% between maximum and minimum were found in the studies from human, dog and rabbit, respectively.

Simple and micro high-performance liquid chromatographic method for simultaneous determination of p-aminohippuric acid and iothalamate in biological fluids.

A simple, rapid and micro high-performance liquid chromatographic method was developed for separate or simultaneous determination of p-aminohippuric acid and iothalamate in plasma and urine using p-aminobenzoic acid as an internal standard. The method involved deproteinizing samples with two volumes of acetonitrile followed by injection of 5 microliters of deproteinized supernatant onto a C18 reversed-phase column. The mobile phase contained 3.

A specific HPLC assay to determine the pharmacokinetics of methotrexate in patients.

The pharmacokinetics of methotrexate and its metabolite, 7-hydroxymethotrexate (7-OH-MTX), were evaluated by a specific HPLC assay in patients receiving low dose (40 mg/m2) or high dose (750-1500 mg/m2) MTX. A wide range of total body clearance (1.03-5.

Evaluation of potential causes for the incomplete bioavailability of furosemide: gastric first-pass metabolism.

Potential causes for reported incomplete (usually 40-60%) and often highly variable (e.g., 11-79%) bioavailability of furosemide in humans were investigated.

Analysis of erythromycin in biological fluids by high-performance liquid chromatography with electrochemical detection.

A simple and sensitive high-performance liquid chromatographic assay was developed for the quantitative determination of major erythromycin components and their potential metabolites or degradation products in plasma and urine. An ether extract of alkalized plasma sample was chromatographed on a reversed-phase column and the components in the column effluent were monitored by an electrochemical detector. The recovery of the drug from extraction was virtually 100%.

Clearance studies of methotrexate and 7-hydroxy-methotrexate in rabbits after multiple-dose infusion.

The concentration-dependent clearance of methotrexate (MTX) and its metabolite, 7-hydroxy-methotrexate (7-OH-MTX), was demonstrated in 5 rabbits using 7 infusion rates (10.5-323 mg/hr). Mean total body clearance (from 34.

Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits after intravenous administration.

The pharmacokinetics of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX), a major metabolite, were investigated in rabbits after intravenous bolus injection and infusion using a specific HPLC assay. The arterial sampling (from the carotid artery) was used in all the studies since peculiar and significant arterial-venous differences in the plasma concentration of MTX and 7-OH-MTX were found following bolus administration of the drug. The disposition kinetics of MTX appeared polyexponential with a small terminal phase having a half-life of 10.