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G Lam

Publications and source records attributed to G Lam.

52 records · Page 3Linked to original sources
PubMed1982

Effect of arterial-venous plasma concentration differences on the determination of mean residence time of drugs in the body.

Using dogs or rabbits as model animals the effect of arterial-venous plasma concentration differences of propranolol, procainamide, griseofulvin, furosemide and theophylline on the determination of mean residence time (MRT) following intravenous administration was evaluated using standard methods. The MRT values calculated from femoral venous data were always higher (ranging from 1.5 to 109%) than those from femoral arterial data. The differences were mainly attributed to the additional residence time of drugs in the sampling tissue (leg). From a physiological point of view it appears generally more logical to assume that only the MRT calculated from arterial data using conventional methods represents the "true" MRT in the body. The potential pharmacokinetic significance of the present findings is discussed. New approaches, which eliminates the effect of arterial-venous plasma concentration differences on the MRT determination, are proposed.

Animals↗
PubMed1982

The significance of the arterial-venous plasma concentration difference in clearance studies.

Arterial-venous blood or plasma concentration differences and their implications for renal clearance studies are reviewed. In common practice peripheral venous blood or plasma is used for absolute clearance studies employing timed-interval methods following single dosing. However, this is theoretically inappropriate or incorrect because of the systemic arterial-venous blood or plasma concentration difference. Many examples showing arterial-venous differences, together with brief theoretical discussions of factors affecting the differences, are presented. The implications in clearance studies of other organs such as lungs, liver, and the gastrointestinal tract are also discussed.

Arteries↗
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↗
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

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↗
PubMed1980

High performance liquid chromatographic analysis of urinary catecholamines employing amperometric detection: references values and use in laboratory diagnosis of neural crest tumors.

We have developed an high performance liquid chromatographic procedure employing amperometric detection for the measurement of urinary free norepinephrine, epinephrine and dopamine. The between-day precision (C.V.) at various concentrations of the above analytes varied from 4.8-11.6%. There was negligible between-urine difference in the percent recovery of norepinephrine and epinephrine but considerable between-urine difference for dopamine. The procedure has been used to determine reference ranges in infants, children and adults. Its preliminary application to the laboratory detection of neural crest tumors is also described.

Adolescent↗
PubMedDate not supplied

Oral and rectal nalbuphine bioavailability: first-pass metabolism in rats and dogs.

The disposition of the narcotic antagonist/analgesic nalbuphine after i.v., oral, and rectal dosing was evaluated in rats and dogs. In both species nalbuphine had high systemic clearance and low oral bioavailability as a result of extensive first-pass metabolism. Administration to a closed 2 cm length of rectum in rats resulted in complete bioavailability; first-pass metabolism was circumvented. However, the extent of first-pass metabolism increased when the dose was not restricted to the lower rectum. Rectal nalbuphine bioavailability in dogs from a solution or three suppository formulations was low and equivalent to oral bioavailability. This was probably because of upward spreading of the dose and subsequent first-pass metabolism. Sodium salicylate, which has been shown to improve rectal absorption of other drugs, did not affect nalbuphine bioavailability rectally.

Administration, Oral↗
PubMedDate not supplied

Phenylpropanolamine pharmacokinetics in dogs after intravenous, oral, and oral controlled-release doses.

An adaption of a published high performance liquid chromatographic (HPLC) assay for phenylpropanolamine (PPA) in plasma was used to examine PPA pharmacokinetics in dogs. Plasma was extracted into ethyl acetate after the addition of 3.5 per cent sodium carbonate, and was then back-extracted into aqueous acetic acid. The acetic acid was injected onto a cyano column using a mobile phase of acetonitrile, dilute hydrochloric acid, and sodium heptane sulfonate. Detection was by UV absorbance at 210 nm. The relative standard deviation of replicate assays averaged 5.2 per cent over a concentration range of 50-1750 ng ml-1 plasma. PPA extraction recovery exceeded 90 per cent. The limit of detection was 30 ng ml-1 using 0.5 ml plasma and injecting 10 microliter. PPA disposition was characterized in three dogs administered PPA i.v. and orally in immediate-release and controlled-release formulations. The terminal elimination half-life averaged 3.5 +/- 0.5 h after the i.v. dose. Oral absorption from the immediate-release capsule was rapid and bioavailability was 98.2 +/- 6.9 per initial rapid cent. PPA absorption from the controlled-release dosage form was biphasic; an rapid phase was followed by a second, slower absorption phase which continued over 16 h. Plasma PPA concentrations then declined with a half-life roughly parallel to the i.v. and oral immediate-release half-lives. Oral bioavailability from the controlled release tablet was 93.7 +/- 5.9 per cent.

Administration, Oral↗
PubMedDate not supplied

Gender differences in glycosylated hemoglobin levels in seasonal affective disorder patients and controls.

Seasonal affective disorder (SAD) has been shown to manifest different symptoms in female and male patients. Specifically, women with SAD have been shown to have greater increases in overeating, weight gain, and increased sleep as compared with their male counterparts. Given these dietary changes, we predicted that female SAD patients would exhibit increased glycosylated hemoglobin (HbA1) levels, indicative of chronically elevated glucose levels. Twenty-two patients (15 women and seven men) and matched controls were enrolled during the winter season and tested for HbA1 levels. A three-way analysis of variance (ANOVA; gender x group x season) was insignificant and the result was a negative study. After the initial hypothesis was rejected, we undertook a post-hoc analysis of the data, from which emerged that in winter, women patients had higher HbA1 levels as compared with matched controls. As our original hypothesis was rejected, we cannot accept the results of the post-hoc study. However, numerous other studies have demonstrated that female and male SAD patients differ in their pathophysiology, and are suggestive that in future analyses ought to consider analyzing subjects separately across gender.

Adult↗