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C M Lai

Publications and source records attributed to C M Lai.

13 recordsLinked to original sources
PubMed1992

Biological activities of recombinant murine interferons alpha 1 and alpha 4: large difference in antiproliferative effect.

The mature forms of two recombinant murine interferons alpha, alpha 1 and alpha 4, have been expressed in vitro using an established transcription and translation system. The relative specific antiviral activity, antiproliferative activity and the natural killer cell stimulating activity of both subtypes were compared in vitro. While the antiviral and natural killer cell stimulating activities of the 2 subtypes were similar, the relative antiproliferative activities varied markedly. On the basis of equal molar inputs, MuIFN-alpha 1 had less than 8% of the antiproliferative activity of MuIFN-alpha 4. This data shows that a large functional difference exists between these two subtypes which are known to be expressed at different levels in mouse L-cells in vitro.

Animals↗
PubMed1979

Urinary excretion of chlorpheniramine and pseudoephedrine in humans.

A specific high-pressure liquid chromatographic method for the determination of chlorpheniramine and pseudoephedrine in urine was developed and applied in a urinary excretion study of normal healthy subjects who received a sustained-release dosage form contianing 8 mgof chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride. Five subjects received one dose on Day 1, followed by multiple dosing every 12 hr for 7 days without ammonium chloride administration. Four subjects received one dose of the sustained-release dosage form together with ammonium chloride. Urine samples were collected during the 1st day and at steady state. The method is specific and simultaneously determines choorpheniramine, two metabolites (mono- and di-desmethylchlorpheniramine), pseudoephedrine, and norpseudoephedrine. The assay recovery was less than 97% (0.06-3 microgram/ml) for chlorpheniramine maleate and less than 98% (1.5-75 microgram/ml) for pseudoephedrine hydrochloride. Excretion of chlorpheniramine and its two metabolites in urine was enhanced after ammonium chloride administration. At steady state, a change in urine pH from 5.69 to 6.46 resulted in more than a 25% decrease in chlorpheniramine and monodesmethylchlorpheniramine excretion. In spite of expected changes in its biological half-life, the overall amount of unchanged pseudoephedrine excreted in urine was not affected by urine pH, presumably because it is primarily excreted in urine as intact drug.

Chlorpheniramine↗
PubMed1979

Effective plasma concentration of N-acetylprocainamide in rats.

Six groups of rats received saline or N-Acetylprocainamide (NAPA) 2--50 mg/kg, intraperitoneally. Thirty minutes later heart rates were measured and simultaneously a blood sample was withdrawn from each rat. There was a linear relationship between plasma concentrations and the administered doses, suggesting linear pharmacokinetics for NAPA. The heart rate was decreased significantly when the average NAPA plasma concentration was 16.8 microgram/ml, which is similar to that found in man.

Animals↗
PubMed1978

Comparative pharmacokinetics of coumarin anticoagulants XXXIII: frequency distribution of dicumarol total clearance in rats.

The total clearance of dicumarol was determined in 172 adult male Sprague-Dawley rats. Clearance values ranged from 1.46 to 27.0 ml/hr/kg. Statistical analysis of a histogram of the total clearance values indicated a trimodal distribution, with modes at 6.28, 14.8, and 23.7 ml/hr/kg. The percentage of animals in each of these components was 60.5, 33.7, and 5.8. A previous study had shown that the total clearance of dicumarol was proportional to the fraction of nonprotein-bound drug in serum (serum free fraction) and that interindividual differences in total clearance of dicumarol in rats were due almost entirely to corresponding differences in the serum free fraction. Therefore, it is likely that the observed trimodal frequency distribution of total clearance values reflects a similar distribution of serum free fraction values of dicumarol. The frequency distribution curve for dicumarol total clearance is very similar to the trimodal frequency distribution curve for warfarin serum free fraction values in rats. This observation is consistent with the previously demonstrated strong correlation of serum free fraction values of dicumarol and warfarin in individual animals.

Animals↗
PubMed1978

Simultaneous determination of pseudoephedrine and chlorpheniramine in pharmaceutical dosage forms.

A simple and sensitive high-pressure liquid chromatographic (HPLC) determination of pseudoephedrine and chlorpheniramine in a pharmaceutical dosage form is described. Quantities of 1.5 microgram of pseudoephedrine and 0.1 microgram of chlorpheniramine are sufficient to determine concentrations in an aqueous solution. Small volume samples, without any extraction procedures, can be treated for direct drug concentration measurement with a high-pressure liquid chromatograph. The stability-indicating property and the accuracy of this method are comparable to those of an established GLC method. The HPLC method can be applied directly and successfully for dissolution studies. The latter application eliminates the need for volume replacement or subsequent mathematical corrections.

Capsules↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXX: Relationship between total clearance and serum protein binding of dicumarol in rats.

The effect of serum protein binding on the elimination kinetics of dicumarol was studied. The serum free fraction of dicumarol was essentially independent of concentration over a wide concentration range and ranged from 0.00015 to 0.00079 in 10 adult rats. The total clearance of dicumarol in these animals ranged from 3.93 to 14.5 ml/kg/hr. As in previous studies, there was an excellent linear correlation between the elimination rate constant for dicumarol and the fraction of dicumarol in the liver (i.e., the amount of drug in the liver divided by the amount of drug in the body). Consistent with theoretical considerations, there was a positive and apparently linear relationship between the total clearance and the serum free fraction of dicumarol. The individual serum free fraction and the fraction in liver values for dicumarol were strongly correlated. The pharmacokinetic model based on a proportional relationship between the apparent elimination rate constant and the fraction in the liver applies to dicumarol but not to warfarin and has limited utility. On the other hand, the model relating total clearance to the serum free fraction has been found to apply to dicumarol, warfarin, and other extensively plasma protein-bound drugs and can be utilized under clinical conditions.

Animals↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXXI: Effect of plasma protein binding on distribution kinetics of dicumarol in rats.

The purpose of this investigation was to determine, with respect to dicumarol, the effect of plasma protein binding on the pharmacokinetic parameters used conventionally to describe the distribution kinetics of a drug on the basis of the time course of its plasma concentration. After rapid intravenous injection, plasma dicumarol concentrations in adult male Sprague-Dawley rats declined triexponentially, with the terminal exponential phase starting at about 4 hr. The free fraction f, of dicumarol in the serum of individual animals ranged from 0.000150 to 0.000790. The parameters of the equation Ct = Pe-pit + Ae-alphat + Be-betat for plasma concentration Ct at time t were obtained by nonlinear least-squares computer fitting of the experimental data and varied appreciably between animals. Of these parameters, only beta showed a significant correlation with f. These observations indicate that the distribution kinetics of this very extensively plasma protein-bound drug, as reflected by the time course of its plasma concentration after intravenous injection, are apparently not affected by intersubject differences in plasma protein binding. There is a remarkable similarity in the valves of P, A, B, pi, and alpha for dicumarol and warfarin, even though the serum free fraction of these drugs differs considerably.

Animals↗
PubMed1976

Relationship between dicumarol distribution and the effect of enzyme induction on dicumarol elimination in rats.

Pronounced intersubject differences in the apparent first-order elimination rate constant (kapp) for dicumarol in rats have been found to be due to corresponding differences in the distribution of dicumarol between the liver (the site of dicumarol biotransformation) and the rest of the body. From theoretical considerations and experimental results in animals given only dicumarol, it has been shown that kapp is linearly related to the fraction of drug in the liver (FL). The proportionality constant (k) for these variables was defined as the intrinsic elimination rate constant for dicumarol which should reflect the activity of the enzyme system(s) involved in the elimination of this drug. The purpose of this investigation was to determine the effect of enzyme induction on dicumarol distribution and on the relationship between kapp and FL in rats. It was found that pretreatment with phenobarbital caused a substantial increase in kapp, but that it had no apparent effect on the serum/liver and serum/kidney concentration ratios of dicumarol. The relative weight of the liver was significantly increased by phenobarbital treatment but the weight of the kidneys was not affected. Linear relationships between kapp and FL were found for both the control and the phenobarbital treated groups, but with a significant difference in the slopes of the regression lines. This study illustrates the application of a pharmacokinetic technique which permits a clear and quantitative distinction between the relative contributions of enzyme activity and body distribution to the in vivo elimination kinetics of a drug.

Animals↗
PubMed1975

Comparative pharmacokinetics of coumarin anticoagulants XV: relationship between pharmacokinetics of dicumarol and warfarin in rats.

The distribution, elimination, and anticoagulant effect of dicumarol and warfarin were determined in adult males rats following intravenous injection of single doses of these drugs in crossover experiments. The biological half-life of dicumarol ranged from 5 to 28 hr; that of warfarin ranged from 9 to 30 hr. There was a statistically significant correlation between the following pharmacokinetic characteristics of dicumarol and warfarin in individual animals: biological half-life, apparent volume of distribution, total plasma clearance, and concentration in plasma eliciting one-half the maximum anticoagulant effect (effective concentration). The mean ratio of the respective biological half-lives (warfarin/dicumarol) was 1.42, and that of the apparent volumes of distribution was 1.50. The ratio of the effective plasma concentrations (dicumarol/warfarin) was correlated negatively with the half-life of dicumarol and positively with the ratio of the half-life values (warfarin/dicumarol) in individual animals. Additional studies with serum samples from other rats showed pronounced interindividual differences in the serum protein binding of both dicumarol and warfarin and a strong correlation between the protein binding of these two drugs in serum of individual animals. The results of this study, together with the results of previous studies in this series, indicate that serum protein binding is the major determinant of interindividual differences in the pharmacokinetics of dicumarol and warfarin in rats under these experimental conditions.

Animals↗
PubMedDate not supplied

Rapid high level production and purification of recombinant murine and human interferons alpha from Escherichia coli.

The availability of large quantities of pure interferon alpha (IFN-alpha) subtypes for in vivo studies has often proved difficult. This paper presents details on the use of the commercially available pGEX expression system for the production and purification of milligram (mg) quantities of recombinant Murine (Mu) and Human (Hu) IFNs-alpha-1 in Escherichia coli. Initially a fusion product is made which can be rapidly purified on a glutathione-sepharose 4B affinity matrix. Biologically active IFN-alpha can then be released from the matrix by cleavage with the restriction protease activated factor X (FXa+7,++). Routine yields of the final products were in the range of 0.5 to 2.0 mg/l of original culture.

Animals↗