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Biomedical subjects

H L Fung

Publications and source records attributed to H L Fung.

At least 145 records · Page 8Linked to original sources
PubMed1981

Kinetics of isosorbide dinitrate and relationships to pharmacological effects.

1 The inter-relationships among oral isosorbide dinitrate (ISDN) dose, drug pharmacokinetics and pharmacological effects were studied in 12 angina patients following single and chronic doses of 15, 30, 60 and 120 mg. 2 Significant accumulation of intact ISDN in plasma was observed after four times a day dosing at 30, 60 and 120 mg for 1 week. 3 The area under the plasma concentration v time curve (AUC), form 0-6 h, was shown to be proportional to dose following single doses. In contrast, AUC increased disproportionately to dose after chronic dosing. 4 Pharmacokinetic correction provided modest improvements in the dose-response relationships of ISDN. 5 Adverse hypotensive effects were observed in five patients after the single 60 mg dose. These patients showed statistically higher AUC and lower intrinsic clearance of ISDN at doses of 15, 30 and 60 mg compared to those who did not develop adverse effects. A possible relationship exists, therefore, between lower drug clearance and hypersensitivity to ISDN.

Adult↗
PubMed1981

Intestinal lead absorption in rats: effects of circadian rhythm, food, undernourishment, and drugs which alter gastric emptying and GI motility.

In rats, the absorption of a 10 mg/kg oral lead dose was reduced by the presence of food in the intestine. In vitro intestinal lead permeability was similar using intestines from fasted or fed rats. No circadian rhythm was apparent in lead absorption or transport across everted rat intestines in vitro. The effects of feeding and circadian rhythm on lead absorption are different from the effects on calcium absorption. Pretreatment of rats with propantheline (5 mg/kg, i.p.) delayed and decreased lead absorption, whereas metoclopramide (10 mg/kg, o.p.) had no significant effect. Lead absorption in undernourished rats, which were allowed only 20-25% of their normal food intake, was similar to control, but the distribution of systemically administered lead was altered.

Animals↗
PubMed1980

Absorption of sodium gamma-hydroxybutyrate and its prodrug gamma-butyrolactone: relationship between in vitro transport and in vivo absorption.

A qualitative relationship between in vitro transport and in vivo absorption of sodium gamma-hydroxybutyrate and gamma-butyrolactone was demonstrated. As with other short-chain acids, sodium gamma-hydroxybutyrate showed capacity-limited transport in vitro, consistent with the previous observation that this drug exhibited slower in vivo absorption with increasing dose. The prodrug lactone, on the other hand, showed a higher intestinal flux than the acid in the everted gut, and in vivo absorption also was more rapid. Capacity-limited transport and absorption of the lactone appeared less evident. Thus, the increased oral hypnotic activity of the lactone over that of the acid most likely is a result of its more favorable intestinal transport characteristics.

4-Butyrolactone↗
PubMed1979

Percutaneous nitroglycerin absorption in rats.

Percutaneous nitroglycerin absorption was studied in shaved rats by monitoring unchanged plasma drug concentrations for up to 4 hr. Drug absorption from the neat liquid state or from an alcoholic solution was considerably poorer than that from a commercial ointment. This observation was unanticipated since the driving force for percutaneous drug absorption was assumed to be drug thermodynamics. Potential artifacts such as drug volatilization from the skin, reduction of surface area through droplet formation, and vehicle occlusion were investigated, but they did not appear to be responsible for the observed results. Two experimental aqueous nitroglycerin gels were prepared with polyethylene glycol 400. One gel contained just sufficient polyethylene glycol to solubilize the nitroglycerin; the other had excess polyethylene glycol to solubilize nitroglycerin far below saturation. Both gels gave extremely low plasma nitroglycerin levels. The composite data suggested that percutaneous nitroglycerin absorption is highly vehicle dependent and that this dependency cannot be explained by simple consideration of drug thermodynamic activity.

Animals↗
PubMed1979

Potency and stability of extemporaneous nitroglycerin infusions.

The potency and stability of extemporaneous intravenous nitroglycerin (NTG) solutions prepared according to methods currently used in three hospitals were studied. Intravenous NTG solutions were prepared and packaged according to three hospitals' protocols. The NTG solutions varied in concentration (32 microgram/ml); source (one of two manufacturers' sublingual NTG tablets or 10% NTG adsorbate in lactose); and storage (ambient room temperature or refrigerated). The concentration of NTG in the i.v. solutions was determined spectrophotometrically. Nitroglycerin was found to be stable for at least 70 days when stored in glass containers, regardless of source, diluent (5% dextrose in water or normal saline) and storage temperature. The loss of NTG from solution, after storage for seven days in plastic i.v. bags, was greater when stored at room temperature (55%) than when refrigerated (30%). Adsorption was shown to be responsible for this phenomenon because intact drug was completely recovered from the plastic i.v. bags after methanol elution. The results of this study allow formulation of recommendations regarding the extemporaneous preparation of i.v. NTG solutions.

Chemistry, Pharmaceutical↗
PubMed1979

Dose-dependent pharmacokinetics and hypnotic effects of sodium gamma-hydroxybutyrate in the rat.

The pharmacokinetics of sodium-gamma-hydroxybutyrate (NaGHB) have been examined as functions of dose and route of administration. The elimination of NaGHB appeared to be controlled by a capacity-limited process which can be described by Michaelis-Menten kinetics. Oral absorption of NaGHB appeared to be fairly extensive in the dose range studied (200-1600 mg/kg), but the peak drug plasma concentrations achieved after oral dosing were relatively low and insensitive to changes in the magnitude of the dose, explaining the lack of pharmacological activity, viz., hypnosis, after oral NaGHB administration even at comparatively high doses. Plasma and brain concentrations were determined at the time when the animals recovered from the hypnotic effects of NaGHB. These concentrations also appeared to be dose-dependent, although the ratio of "waking" plasma to brain concentration was constant with respect to dose.

Administration, Oral↗
PubMed1978

Validity of oral bioavailability estimates of phenolsulfonphthalein based on total urinary excretion from rats.

Urinary recovery of phenolsulfonphthalein from rats were determined after intracardial (0.075 mg) and oral (1.5 mg) doses. Although trace quantities of conjugated metabolites could be identified by TLC, the levels present did not introduce significant error into estimates of total phenolsulfonphthalein excretion if samples were assayed directly by colorimetric methods for only unchanged dye. The absolute availability of phenolsulfonphthalein based on urinary recovery under the present experimental conditions was estimated at 10.6%.

Administration, Oral↗
PubMed1978

Improved GLC determination of plasma nitroglycerin concentrations.

A specific and quantitative assay for determining nanogram levels of nitroglycerin in plasma was developed. The method involves stabilization of the drug in plasma with silver nitrate, followed by multiple extraction using purified hexane. Isosorbide dinitrate is added as the internal standard. The hexane extract is subsequently concentrated and injected into a glass column packed with 3% SP-2401 on 100--120-mesh Supelcoport at 140 degrees. A 63Ni-electron-capture detector gives a linear response over the range of 0.1--50 ng of nitroglycerin/ml of rat plasma. From spiked samples, the procedure gave a recovery of about 90%. There was little or no interference from the isomeric glyceryl dinitrates and endogenous compounds in rat or human plasma.

Animals↗
PubMed1978

Pharmacokinetics of nitroglycerin in rats.

The plasma nitroglycerin levels obtained after intracardial (0.7 mg/kg), oral (7 mg/kg), and topical (7--14 mg/kg) doses of nitroglycerin in rats are reported. Nitroglycerin followed essentially one-compartment kinetics after intracardial administration, showing a mean half-life of about 4 min and a mean apparent volume of distribution of about 3 liters/kg. After oral drug administration, "flip-flop" kinetics were evident. The mean oral bioavailability was determined to be 1.6%, firmly supporting the contention that nitroglycerin is extensively metabolized during first passage through the liver. Under the experimental conditions studied, no detectable levels of nitroglycerin were observed after topical application.

Administration, Oral↗
PubMed1978

Molecular interaction between E-prostaglandins and selected polymers and its potential utilization in oral dosage form design.

Coacervate formation was observed between some E-prostaglandins and povidone in acetonitrile. This molecular interaction was studied using differential scanning calorimetry, IR spectrophotometry, and light microscopy. The structural requirements for coacervate formation between E-prostaglandins and povidone were investigated. Possible utilization of this molecular interaction in the development of E-prostaglandin formulations was explored. The dissolution rate of some insoluble E-prostaglandin esters increased when they were coprecipitated with povidone and polyethylene glycol. For example, the p-hydroxybenzaldehyde semicarbazone ester of 16,16-dimethyldinoprostone dissolved about 200 times faster as a povidone coprecipitate than did the control mixture. Enhancement of the dissolution rate was observed for the povidone coprecipitates of dinoprostone and its p-acetylphenyl and beta-naphthyl exters but not for the p-phenylphenyl ester. Fast dissolving dispersions of the E-prostaglandin esters also could be prepared with the water-insoluble cross-linked polyvinylpyrrolidone. This type of dispersion was nonglassy and easily dispersible in water. Thus, it might have certain advantages over the classical soluble povidone coprecipitates in terms of ease of handling. The degree of enhancement in dissolution of dispersions of cross-linked polyvinylpyrrolidone and E-prostaglandin esters is apparently dependent on the structure of the esters. The potential dissolution enhancement may be related to the strength of the interaction between the macromolecule and the esters, as indicated by the qualitative relationship between the extent of adsorption of the prostaglandins to cross-linked polyvinylpyrrolidone and the dissolution rate enhancement.

Administration, Oral↗