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Biomedical subjects

W L Chiou

Publications and source records attributed to W L Chiou.

At least 91 records · Page 5Linked to original sources
PubMed1982

Digoxin pharmacokinetics in premature infants.

An analysis of pharmacokinetic parameters of digoxin was carried out in six premature infants after the administration of a single total digitalizing dose of 20 microgram/kg. The data was analyzed using both a 2 and 3 exponential model. In the premature infant, the plasma half-life of digoxin is prolonged, while the volume of the central compartment, total body clearance, volume of distribution and volume of distribution at steady state are reduced compared to other aged patients.

Digoxin↗
PubMed1982

Creatinine X--potential nonrenal elimination of endogenous creatinine in humans and its clinical significance.

From an analysis of the data in the literature for creatinine renal clearance and steady-state serum level and published equations, we estimated a wide range (1.4-76.3 ml/min) of nonrenal clearances of endogenous creatinine. Nonrenal clearance might contribute 0-34% of the total body clearance in patients with normal renal function. This paper discusses the clinical significance of the potential overestimation of renal function by using published nomograms or equations (derived from a direct inverse relationship between the creatinine clearance and steady-state level or the assumption of nonexistence of nonrenal elimination of creatinine) for indirect estimation of creatinine clearances from serum creatinine levels.

Creatinine↗
PubMed1982

Absorption of oral neomycin in premature infants with suspected necrotizing enterocolitis.

The oral absorption of neomycin was studied in 2 premature infants (32 weeks of gestation) with suspected necrotizing enterocolitis. 1 infant received 50 mg and the other 100 mg of neomycin sulfate/kg/day in 4 divided doses for approximately 7 days. Plasma neomycin levels were determined by a micro, sensitive and specific high-performance liquid chromatographic assay developed in our laboratory. Plasma levels as high as 2.9 and 4.5 micrograms/ml were observed in these 2 infants. A urinary recovery study for 1 infant revealed that at least 3.7% of the oral dose was absorbed. The significant and persistent plasma levels of neomycin in these patients suggest the need for extreme caution in using this potentially toxic antibiotic for prolonged treatment in neonates.

Chromatography, High Pressure Liquid↗
PubMed1981

Sensitive and rapid high-performance liquid chromatographic method for the simultaneous determination of methotrexate and its metabolites in plasma, saliva and urine.

A simple and sensitive high-performance liquid chromatographic assay of methotrexate (MTX) and its two active metabolites, 7-hydroxymethotrexate (7-OH-MTX) and and 2,4-diamino-N10-methylpteroic acid (APA) in plasma, saliva and urine was developed. The method involved deproteinization with acetonitrile followed by addition of isoamyl alcohol and ethyl acetate. After extraction the sample was chromatographed on a cation-exchange column and monitored at 313 nm. The retention times were 5, 7 and 9 min and detection limits 20, 10 and 5 ng/ml for 7-OH-MTX, MTX and APA, respectively. For concentrations greater than 100 ng/ml one-step deproteinization of 0.1 ml sample with 0.25 ml acetonitrile was satisfactory for sample preparations. The method has been evaluated in samples from patients and rabbits receiving MTX.

Animals↗
PubMed1981

Instantaneous input hypothesis in pharmacokinetic studies.

Observed venous plasma concentrations of furosemide, propranolol, griseofulvin, and theophylline at 0.33 and 0.66 min after intravenous bolus injections to unanesthetized dogs were compared with those extrapolated using the instantaneous input hypothesis. At 0.33 min, extrapolated/observed plasma level ratios as high as 20.5, 65.5, 226, and 1.17 were found for these four drugs, respectively. Venous plasma levels peaked at 1 min postinjection in all studies. Total plasma areas (AUC0-->infinity) estimated using the instantaneous input principle were higher by as much as 6.0, 6.8, and 19.6% for propranolol, griseofulvin, and furosemide, respectively, when compared with experimental data. The effect on theophylline was negligible. These results suggest the need for cautious interpretation of some venous pharmacokinetic data. More studies in animals and humans are required to assess the magnitude of deviation from the instantaneous input hypothesis for drugs in general.

Animals↗
PubMed1981

The clinical pharmacokinetics of buflomedil in normal subjects after intravenous and oral administration.

A dose-ranging pharmacokinetic study of buflomedil was carried out in eight subjects to determine the pharmacokinetic parameters of the drug after oral and intravenous administration. Based on AUC infinity analyses, the pharmacokinetics of buflomedil were found to be linear within the dose ranges studied (50 to 200 mg for i. v. injection and 150 to 450 mg for oral administration). In the oral study, the mean biological half-life of the drug was 2.97 h, while after intravenous dose it was 3.25 h. The apparent volume of distribution after the pseudodistribution equilibrium (Fd beta) and volume of distribution at the steady state (Vdss) were 1.43 +/- 0.24 l/kg and 1.32 +/- 0.26 l/kg, respectively. The mean urinary recovery of intact drug and the metabolite, paradesmethyl buflomedil, after intravenous dosing, were 23.6% and 18.7%, respectively, while after oral dosing, they were 18% and 14.8%, respectively. On the average, 72% of the dose was observed into the systemic circulation after oral administration. This level of bioavailability was attributed to the hepatic first-pass effect.

Administration, Oral↗
PubMed1981

Pharmacokinetics and tissue distribution of chlorpheniramine in rabbits after intravenous administration.

Intravenous studies of chlorpheniramine (CPM) were conducted in six New Zealand White male rabbits (mean wt. 3.88 kg). CPM and its two demethylated metabolites in arterial serum and urine were assayed by HPLC. Triexponential equations were needed to fit the i.v. CMP serum data in three rabbits, while biexponential equations were required in the other three rabbits. Harmonic mean of V1, Mss, Varea, CL, and terminal t 1/2 were 2.84, 10.8, and 15.5 liters/kg, and 4.14 liters/kg/hr and 2.57 hr, respectively. The average serum protein binding was 44%. The average blood to plasma concentration ratio was 1.85. Estimated mean hepatic blood extraction ratio based on i.v. studies was 0.88. Tissue distribution studies showed rapid and extensive uptake of CPM by various organs such as lung, kidneys, and brain after i.v. bolus injection, and their concentrations were 160-, 80-, and 31-fold higher than the plasma level. The amount of CPM in the muscle was calculated to represent about 50% of CPM present in the body near the steady state. Variation in plasma protein and tissue binding was postulated to be an important factor for the observed marked interspecies difference in the apparent volume of distribution of CPM. Only 2% of the dose was excreted unchanged in the urine.

Animals↗
PubMed1981

Oral absorption and presystemic first-pass effect of chlorpheniramine in rabbits.

The oral absolute bioavailabilities of chloropheniramine (CPM) in four rabbits (New Zealand White, male, mean wt. 3.71 kg), averaged 0.06 +/- 0.03, 0.11 +/- 0.08, and 0.09 +/- 0.01 following a 3, 10.5, and 21 mg/kg dose, respectively. The individual bioavailability data and the AUC of one of the demethylated metabolites, desdimethyl CPM (DDCPM) obtained following different doses suggested the existence of saturable presystemic elimination. Two rabbits received an additional 10.5 mg/kg dose of CPM through portal vein infusion. Based on the oral, intraportal vein and i.v. studies, the mean extraction ratios of gut and the liver calculated for these two rabbits averaged 0.58 and 0.76, respectively. The latter value agreed well with the estimated hepatic extraction ratio from the in vitro liver homogenate study (0.89) or from the i.v. studies (0.83). The existence prehepatic first-pass effect observed in the present study was consistent with similar findings in humans and dogs.

Administration, Oral↗
PubMed1981

Arterial and venous blood sampling in pharmacokinetic studies: propranolol in rabbits and dogs.

Significant and persistent arterial-venous (A-V) plasma concentration differences of propranolol in unanesthetized rabbits and dogs following intravenous bolus injection or intravenous infusion were found. Both arterial and venous data were then subjected to extensive pharmacokinetic analyses utilizing standard procedures. Marked differences in calculated noncompartmental pharmacokinetic parameters such as the steady-state volume of distribution, absolute amount present in the body, and relative contribution of the terminal phase were obtained. The appropriateness of using venous propranolol plasma data for multicompartmental mammillary pharmacokinetic modeling analysis was discussed. The significance of the present study in pharmacokinetic and pharmacodynamic investigations of propranolol in humans remains to be explored.

Animals↗
PubMed1981

Arterial-venous plasma concentration differences of six drugs in the dog and rabbit after intravenous administration.

The arterial blood from the femoral artery and venous blood from the femoral vein wee simultaneously collected following intravenous administration of propranolol, lidocaine, procainamide, furosemide, theophylline and griseofulvin to dogs or rabbits. The preliminary results of arterial-venous (A-V) plasma concentration profiles are reported in this communication. The maximum A/V ratios shortly after a rapid intravenous bolus dose were 277-, 15-, 34-, 33-, 5.4- and 3240-fold, respectively, for the above six drugs. The venous plasma levels were higher than arterial plasma levels during parallel terminal phase by as much as 104, 48, 134, 29, 16, and 47%, respectively, for the above six drugs. These data suggest a very rapid and extensive uptake of the drugs by the sampling tissues (the leg) shortly after dosing. The potential significance of A-V differences in pharmacokinetic and pharmacodynamic studies are briefly discussed.

Animals↗
PubMed1981

Pharmacokinetics of drugs in blood II. Unusual distribution and storage effect of furosemide.

Furosemide was found to exhibit both in vitro and in vivo unusual distribution kinetics in whole blood. For example, at an initial blood concentration of 10 microgram/ml, a 'trough' plasma level phenomenon occurring at 5 min was found in the in vitro study using blood from humans, rabbits, and dogs. A similar effect was also observed in rabbits following intravenous dosing. The effect of the time elapsed between blood collection and centrifugation on the measured plasma level, the so called 'blood storage effect' was clearly demonstrated in rabbit studies. A difference of up to 32% was found. Furosemide was found to be stable in blood, and the equilibrium plasma/blood cell concentration ratios were about 1.5-2.0 at 0.1-50 micrograms/ml in blood.

Animals↗
PubMed1981

The physiological significance of the apparent volume of distribution, Vdarea or Vd beta, in pharmacokinetic studies.

The definition and significance of the Vdarea or Vd beta are studied based on the physiological clearance or pharmacolinetic modeling theory. It was found that the Vdarea calculated by dividing the intravenous dose by the beta. AUC. (where beta is the terminal phase exponential rate constant and AUC is the total area under the systemic arterial or venous plasma concentration vs. time curve from time zero to time infinity) can only serve as a proportionality constant to relate the total amount of compound present in the body and its systemic arterial plasma concentration during the terminal phase. Its use with the systemic peripheral venous plasma concentration may result in a significant overestimation of the amount present in the body because of the existence of the potential arterial-venous plasma concentration difference. The above new definition of the V can also be applicable to compounds undergoing the pulmonary first-pass elimination.

Humans↗
PubMed1980

New calculation method of mean total body clearance of drugs and its application to dosage regimens.

A new method for calculating the mean total body drug clearance is proposed for determining the mean dosing rate for patients. In this method, the mean clearance can be calculated from the individual clearance values by the harmonic mean method, or it can be determined by dividing the same absorbed dose by the arithmetic mean of the areas under the plasma level-time curve from time zero to infinity from all of the subjects or patients studied. In this method, the arithmetic mean method is assumed to have been used for calculation of literature mean plasma levels. Various methods for calculating mean clearances also are evaluated. These methods yield different mean clearance values from the same set of individual data, resulting in different dosage regimen recommendations.

Kinetics↗