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Biomedical subjects

E Doyle

Publications and source records attributed to E Doyle.

At least 109 records · Page 6Linked to original sources
PubMed1981

Pharmacokinetics of isosorbide dinitrate in rhesus monkey, cynomolgus monkey, and baboon.

At 2 min after intravenous injection of isosorbide dinitrate (1 mg/kg), mean plasma drug concentrations were 565 +/- 66 (SD), 586 +/- 43, and 1572 +/- 253 ng/ml in the rhesus monkey, cynomolgus monkey, and baboon, respectively. Following a relatively short distribution phase, mean plasma concentrations declined with half-lives of 62, 23, and 24 min in these three species, respectively. The time course of plasma concentrations could be described by a two-compartment open model, although a one-compartment open model was adequate for obtaining some pharmacokinetic parameters. Statistically significant differences among the species were observed in areas under the plasma concentration-time curves, plasma half-lives, and volumes of distribution. The pharmacokinetics kinetics of isosorbide dinitrate in baboons most closely resembled those in humans.

Animals↗
PubMed1981

Comparative pharmacokinetics of antipyrine (phenazone) in the baboon, cynomolgus monkey and rhesus monkey.

The pharmacokinetics of antipyrine (phenazone) in 3 species of non-human primate have been evaluated following its intravenous administration at a dose level of 92 mg/kg. Mean peak plasma concentrations of antipyrine of 132, 137 and 155 microgram/ml in the rhesus monkey, the cynomolgus monkey and the baboon respectively were not observed until 5 min after intravenous injection. Thereafter, concentrations declined with an apparent half-life of elimination of 1.5-2 h. The time-course of plasma antipyrine concentrations was adequately described by a one-compartment open model and no notable differences in pharmacokinetic parameters utilising a 2-compartment open model were observed. Antipyrine was mainly distributed in total body water. The mean volume of distribution was equivalent to 88, 73 and 66% of body weight in rhesus monkey, the cynomolgus monkey and the baboon, respectively. An analysis of variance of volumes of distribution, apparent half-lives of elimination and systemic clearances showed that there was a statistically significant species-related difference in systemic clearance (P less than 0.05) and volumes of distribution (P less than 0.01) which were lower in the cynomolgus monkey than in the other 2 species. The pharmacokinetics of antipyrine in the non-human primate are more similar to those of other laboratory animal species than to those of humans.

Animals↗
PubMed1978

Benign tumors of right atrium necessitating extensive resection and reconstruction.

Two patients with gigantic benign right atrial tumors were successfully treated at New York University Medical Center. Both patients required extensive resection and reconstruction for cure. Although these tumors are rare, thorough exploration employing cardiopulmonary bypass is required before an appraisal of resectability can be made. Reconstruction can be readily accomplished with autologous pericardium and thereby provides an opportunity for cure of these unusual and rare lesions.

Adult↗
PubMed1976

Serum concentrations of methaqualone after repeated oral doses of a combination formulation to human subjects.

Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 mug/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and thereafter more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 mug/ml; 1.5 mug/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 mug/ml - 0.6 mug/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation.

Administration, Oral↗
PubMedDate not supplied

Measurement of plasma concentrations of isosorbide dinitrate.

Concentrations of the vasodilator isosorbide dinitrate (ISDN) in human plasma can be measured with good sensitivity (about 0.2--0.5 ng ml-1) using electron-capture gas chromatography after a one-stage extraction. The mean recovery of ISDN from plasma was 83 per cent +/- 9 standard deviation (S.D.). The precision of the method for the measurement of ISDN in plasma ranged from +/- 14 per cent at 1 ng ml-1 to +/- 7 per cent at 5 ng ml-1 to +/- 4 per cent at 50 ng ml-1. The 95 per cent confidence limits of the least-squares regression calibration line forced through the origin were +/- 100 percent at 1 ng ml-1, +/- 11 per cent at 10 ng ml-1, and +/- 8 per cent at 30 ng ml-1. The method has been used to assay many samples withdrawn after doses of drug at therapeutic levels to normal subjects.

Chromatography, Gas↗
PubMedDate not supplied

Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects.

Plasma concentrations of isosorbide dinitrate have been measured after intravenous infusion of drug at a rate of 5.0 mg h-1 for 150 min and after single equal oral doses of 12.5 mg of drug in solution to two normal human subjects. During the infusion, uneven plateau concentrations were approached after 30 min. The calculated average steady-state plasma levels were 258 ng ml-1 and 514 ng ml-1 in the two subjects respectively. The half-life of elimination of isosorbide dinitrate after termination of the infusion was 9--10 min. After oral doses, peak plasma levels of 26.6 ng ml-1 and 12.7 ng ml-1 occurred at 10 min and 20 min in the two subjects respectively. The terminal half-life of drug after the oral doses was much longer than the elimination half-life (about 10 min), and was associated with the absorption phase. Fairly good agreement was obtained between the observed concentrations and those predicted by a one-compartment open model. The systemic availability of isosorbide dinitrate after the oral doses was up to only 3 per cent of the equal doses infused, indicating that presystemic elimination processes accounted for very large proportions of the oral doses. The systemic clearances of drug after infusion of 0.32 l min-1 and 0.16 l min-1 were unexpectedly low for a drug of reported high liver extraction ratio.

Adult↗
PubMedDate not supplied

Isosorbide 5-mononitrate pharmacokinetics in humans.

When isosorbide 5-mononitrate was intravenously infused at a rate of 4 mg h-1 for 2.5 h to five human subjects, its concentrations in plasma increased slowly to 185 ng ml-1 +/- 5 per cent C.V. at 2.5 h and a steady-state plasma level was not reached during the infusion. When the infusion was discontinued, plasma drug concentrations declined with an elimination half-life of 4.2 h +/- 6 per cent C.V. The systemic clearance after the infusion doses was 132 ml min-1 +/- 18 per cent C.V. and the volume of distribution was 48.4 +/- 16 per cent C.V. After equal oral doses of 10 mg, the peak plasma isosorbide 5-mononitrate concentration of 191 ng ml-1 +/- 16 per cent C.V. was reached at 1.1 h +/- 30 per cent C.V., and plasma levels declined with a terminal half-life of 4.9 h. The complete systemic availability of isosorbide 5-mononitrate indicated that pre-systemic elimination after the oral doses was negligible. A one-compartment open model appeared adequate to describe the plasma level data after intravenous infusion and oral dose. After single oral doses of 10 mg isosorbide dinitrate, the peak plasma concentration of the 5-mononitrate metabolite of 72 ng ml-1 +/- 27 per cent C. V. occurred at 1.7 h +/- 41 per cent C.V. Approximately 50 per cent (range 22--68 per cent) of the oral dose of isosorbide dinitrate circulated in plasma as the 5-mononitrate metabolite. The pharmacokinetics of isosorbide mononitrates are markedly different to those of the parent dinitrate and these differences follow from the greater systemic availability and volume of distribution of the mononitrates.

Adult↗
PubMedDate not supplied

Plasma concentrations and bioavailability of isosorbide dinitrate and pindolol from a combination formulation.

The plasma concentrations and bioavailability of sustained-release isosorbide dinitrate and standard-release pindolol have been compared after administration of these drugs in combination and alone. Bioavailability parameters of isosorbide dinitrate and pindolol obtained after administration of the drugs in combination were not significantly different (P greater than 0.05) to those obtained after administration of either drug alone. Two peaks of mean concentrations of isosorbide dinitrate occurred in plasma after administration of 30 mg of this drug in combination with 7.5 mg pindolol (4.4 ng ml-1 at 1 h and 4.5 ng ml-1 at 5 h), or alone (5.9 ng ml-1 at 2 h and 5.7 ng ml-1 at 5 h). In each case, plasma concentrations of isosorbide dinitrate were maintained during at least 8 h, whereas the drug was not detected in plasma at 2.5 h after administration of a standard-release formulation. The peaks of mean concentrations of pindolol were 39.7 ng ml-1 at 1.5 h after administration of 7.5 mg drug in combination with isosorbide dinitrate and 38.0 ng ml-1 at 1 h administration of the drug alone. Concentrations of pindolol in plasma declined with a half-life of 3 h.

Adolescent↗
PubMedDate not supplied

Plasma concentrations of isosorbide dinitrate after cutaneous and sublingual doses to human subjects.

After application of 100 mg (nominal dose) isosorbide dinitrate as an ointment to the skin of human subjects, mean drug concentrations were 1 to 2 ng/ml for 1.5 hour and reached a peak of 6.2 ng/ml at 6 hours. Thereafter, mean concentrations declined slowly to 2.9 ng/ml at 12 hours and 1.2 ng/ml at 24 hours. After a sublingual dose of 5 mg isosorbide dinitrate, mean drug concentrations reached a peak of 15.9 ng/ml at 0.5 hour and declined with a half-life of about 50 minutes. The mean bioavailability of isosorbide dinitrate from the ointment was estimated as 30 per cent of that from the sublingual tablet when corrected for differences in dose/body weight ratio. The results demonstrate that concentrations of isosorbide dinitrate in plasma can be maintained for relatively long periods when the drug is applied to the skin.

Administration, Topical↗
PubMedDate not supplied

Transport of the critically ill child.

The principles of stabilization before, and monitoring during, transportation are well established in adult intensive care practice but less so in paediatrics. The speed with which critically ill children deteriorate and the aggressiveness of treatment needed are often underestimated. A dedicated, fully funded and staffed transport service for each paediatric referral centre in the UK is urgently required.

Child↗