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Biomedical subjects

R F Palmer

Publications and source records attributed to R F Palmer.

At least 55 records · Page 3Linked to original sources
PubMed1977

Ethanol and oral diazepam absorption.

Despite widespread use and abuse of ethanol and diazepam in combination, little is known about the effects of ethanol on diazepam absorption. We administered diazepam (0.07 mg per kilogram of body weight) with water and with 30 ml of 50 per cent ethanol to seven normal volunteers. Plasma diazepam levels were significantly higher at 60 minutes (P less than 0.05), 90 minutes (P less than 0.01), 120 minutes (P less than 0.01), and 240 minutes (P less than 0.01) when diazepam was administered with ethanol than with water alone. Since maximum mean plasma diazepam levels after combined ingestion with ethanol were nearly twice as high than after diazepam and water (373 ng per milliliter versus 197 ng per mililiter at 60 minutes) we conclude that ethanol enhanced diazepam absorption.

Administration, Oral↗
PubMed1977

The measurements of propantheline ion in biological fluids after administering propantheline bromide to man.

The measurement of propantheline ion has been accomplished in urine and plasma following administration of propantheline bromide to man. Trideuteropropantheline bromide is added to the biological fluid to act as a carrier and internal standard to quantify the propantheline ion using multiple ion monitoring. Methane was used as reactant gas but following the discovery of exchange of the trideuteromethyl group when using methane, ammonia was used for later analyses. The determination of propantheline ion in urine and plasma after administration of propantheline bromide to man is described.

Deuterium↗
PubMed1977

Factors influencing comparative bioavailability of spironolactone tablets.

The bioavailability of spironolactone from 10 tablet formulations, selected to provide a wide range of specifications and in vitro dissolution rates, was assessed from the plasma and urinary levels of its major unconjugated metabolite, canrenone, in a study of balanced incomplete block design using 11 healthy subjects. Significant but weak correlations existed between the amount of spironolactone in solution at 40 min in vitro and the area under the plasma concentration-time curve for canrenone and urinary canrenone excretion. The correlations between in vitro dissolution and bioavailability parameters appeared to be weakened by two tablet formulations, one with dibasic calcium phosphate as the principal excipient and the other formulated from micronized spironolactone bulk drug. Measurement of in vitro dissolution of spironolactone tablets is of value for quality control purposes, provided no major alteration is made in the formulation.

Adult↗
PubMed1977

Validation of plasma and urinary canrenone for determination of bioavailability of spironolactone--comparison of tablets with solution/suspension.

Data showing a linear relationship between spironolactone dose and the levels of canrenone in plasma and urine are presented to support the use of canrenone levels as a measure of the bioavailability of spironolactone. The bioavailability of a selected batch of spironolactone 25 mg tablets was compared to that of an oral aqueous suspension of spironolactone in a separate balanced cross-over study involving 10 healthy subjects. The tablets were equivalent to suspension as regards area under the plasma concentration-time curve and total urinary excretion of canrenone, the prinicipal unconjugated metabolite of spironolactone. Peak plasma concentrations of canrenone were higher, and were attained significantly earlier, after treatment with spironolactone in suspension. The results indicate that spironolactone was absorbed more rapidly from the suspension, but that the total absorption did not differ between the two formulations.

Administration, Oral↗
PubMed1972

The effect of sulfonylurea drugs on rabbit myocardial contractility, canine purkinje fiber automaticity, and adenyl cyclase activity from rabbit and human hearts.

Long-term clinical studies have associated tolbutamide therapy with an increased incidence of cardiovascular deaths. The effects of this and other sulfonylurea drugs on contractility and rate of isolated rabbit atria, automaticity of isolated dog Purkinje fibers, and adenyl cyclase activity in particulate preparations of rabbit and human hearts were studied. At concentrations that are attained clinically, tolbutamide (10 mg/100 ml) increased contractility of driven rabbit atria to 124+/-5% of control, acetohexamide (3.9 mg/100 ml) to 140+/-5%, chlorpropamide (8.3 mg/100 ml) to 139+/-6%, and tolazamide (3.1 mg/100 ml) to 119+/-6%. These effects were accentuated in the presence of 2.5 x 10(-4) M theophylline and were not blocked by 1 x 10(-5) M propranolol. Adenyl cyclase was activated by each of these drugs at concentrations below those which increase contractility. The drugs also increased the rate and slope of phase 4 depolarization in spontaneously beating Purkinje fibers, but did not alter the spontaneous rate of isolated rabbit atria. Since inotropic and chronotropic stimulation can be deleterious in some clinical settings, these findings may be of significance in interpretation of cardiovascular mortality data.

Acetohexamide↗