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Biomedical subjects

E J Triggs

Publications and source records attributed to E J Triggs.

At least 37 records · Page 2Linked to original sources
PubMed1988

High-performance liquid chromatographic assay of cefotaxime, desacetylcefotaxime and ceftriaxone in rat plasma.

A simple and selective high-performance liquid chromatographic method is described for the analysis of the cephalosporins cefotaxime (CXM), desacetylcefotaxime (DACXM) and ceftriaxone (CFX) in rat plasma. Plasma was deproteinized with methanol, and the supernatant was directly injected into the chromatograph and monitored at 254 nm. For determination of the unbound drugs, a centrifugal ultrafiltration method was employed. The calibration curves were linear (r = 0.999) from 2.5 to 500 micrograms/ml; the detection limits were 100 ng/ml for DACXM and 250 ng/ml for CXM and CFX. The method was not interfered with by other plasma components, nor by barbital sodium or caffeine, and has been applied to study the pharmacokinetics of the cephalosporins in rats.

Animals↗
PubMed1985

The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites.

The disposition of a low dose (600 mg) of acetylsalicylic acid (ASA) and its metabolites (salicylate, salicyluric acid and salicyl glucuronides) was studied in 25 male and female patients of different ages. Plasma levels of ASA and salicylate were found to be significantly higher in the females (young and elderly), whereas plasma levels of salicyluric acid were found to be significantly higher in the elderly (male and female) groups. The higher plasma levels of ASA and salicylate in the females appear to be due to an intrinsically lower metabolic activity in that sex, while the lower clearance of salicyluric acid leads to the accumulation of that compound in the aged. No age and sex effects were found to influence the volumes of distribution of ASA, salicylate and salicyluric acid.

Adult↗
PubMed1984

Comparison of plasma levels of canrenone and metabolites after base hydrolysis in young and elderly subjects following single and multiple doses of spironolactone.

Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and significant differences were found between the two age groups in the AUC for both canrenone and 'total metabolites'. However, these differences between the two age groups diminished after multiple dosing on Day 8, and the steady state pre-dose plasma levels of canrenone and 'total metabolites' were significantly higher in the elderly subjects. The accumulation ratios of canrenone and 'total metabolites' were significantly higher in the elderly than in the young subjects. Both canrenone and canrenoic acid were extensively bound to plasma protein, but no differences were found between the two age groups in protein binding. Observed differences in plasma levels after single and multiple dosing between young and old subjects may be consequences of many factors such as a proportionate shift in metabolism with age; impaired oral absorption of the parent compound; and/or altered volume of distribution of the drug.

Adult↗
PubMed1984

Pharmacokinetics of canrenone and metabolites after base hydrolysis following single and multiple dose oral administration of spironolactone.

The pharmacokinetics of canrenone and 'total metabolites' after base hydrolysis was studied in eight young volunteers following single and multiple dose oral administration of spironolactone. The plasma levels of canrenone and 'total metabolites' were fitted to a two-compartment open model with a first-order absorption process. From our eight normal subjects studied, the harmonic mean of the distributive half-life (t1/2 alpha) of canrenone was found to be 1.66 h, and the harmonic mean of the terminal elimination half-life (t1/2 beta) to be 22.6 h. Harmonic means of the distributive and elimination half-lives of 'total metabolites' after base hydrolysis were 2.48 h and 28.8 h respectively. The accumulation ratio of canrenone was 2.53, whereas that of 'total metabolites' was 1.89. Despite the fact that spironolactone has been shown to induce hepatic metabolism of other drugs, no evidence of autoinduction was noted in the present study, as plasma levels of canrenone and 'total metabolites' were found to obey a linear two-compartment model with reproducible absorption and disposition after single and multiple doses.

Administration, Oral↗
PubMed1984

Pharmacokinetic and pharmacodynamic modelling with pancuronium.

The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent ( NMBA ) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79 +/- 0.28 ml X min-1 X kg-1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. Plasma concentration and % paralysis data were successfully fitted to a previously proposed pharmacodynamic model. This model assumes a separate effect compartment which exchanges drug directly with the central kinetic compartment (integrated effect model). The 'steady-state' Cp necessary to produce 50% paralysis ( ECpss (50] was estimated to be 0.21 +/- 0.08 micrograms X ml-1 (mechanical response) and 0.18 +/- 0.05 micrograms X ml-1 (EMG response). An analysis using the Hill equation of the Cp-response relationship, during and after the constant-rate infusion of pancuronium bromide, resulted in effective plasma concentrations for 50% paralysis ( ECp50 ) of 0.35 +/- 0.06 micrograms X ml-1 and 0.20 +/- 0.09 micrograms X ml-1, respectively, for mechanical twitch response. The corresponding values for EMG response were 0.32 +/- 0.06 micrograms X ml-1 and 0.17 +/- 0.06 micrograms X ml-1. Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p less than 0.05); no such difference was apparent between this latter parameter and the ECpss (50) of the integrated effect model (p greater than 0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p greater than 0.05).

Adult↗
PubMed1984

Pharmacokinetics of alcuronium in elderly patients undergoing total hip replacement or aortic reconstructive surgery.

The pharmacokinetic behaviour of alcuronium was studied in three patients undergoing resection of an aortic aneurysm, and in another two patients undergoing total hip replacement (group I). A control group of five elderly patients undergoing relatively minor surgery was included (group II). In group I patients, the values of the pharmacokinetic parameters such as plasma clearance, elimination half-life and the apparent volume of distribution of the drug were found to be comparable to those obtained in normal young patients in previous studies. The group II patients, however, were found to have a prolonged elimination half-life as a result of reduced plasma clearance, possibly an age-related effect. The differences between these two groups of patients may be explained by the differences in the extent of haemorrhage and fluid replacement or changes in blood circulation, or both. However, alcuronium must still be used cautiously in both groups of patients, especially in the light of a recent finding that patients undergoing aortic reconstructive surgery have a high frequency of functional renal failure after operation.

Aged↗
PubMed1983

Chronic propranolol administration during pregnancy. Maternal pharmacokinetics.

The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p much greater than 0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30-160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p = 0.072, df = 13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p less than 0.05, df = 13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.

Adult↗
PubMed1983

Metabolism of propranolol in the human maternal-placental-foetal unit.

Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous maternal plasma levels for propranolol and its major metabolites (mean +/- SD) were: propranolol 0.32 +/- 0.17, propranolol glucuronide 0.86 +/- 0.36, 4-hydroxypropranolol 1.4 +/- 1.0, 4-hydroxypropranolol glucuronide 0.71 +/- 0.45 and naphthoxylactic acid 3.0 +/- 1.6. P binding in cord plasma at delivery was 67.2 +/- 3.9% (mean +/- SD) which was significantly less ('t' = 13.4, df = 13, p less than 0.001) than the P binding in maternal plasma at delivery (87.5 +/- 1.6%, mean +/- SD). The plasma protein binding (mean +/- SD) of naphthoxylactic acid in cord plasma (98.6 +/- 0.2%) was significantly greater ('t' = 3.808, df = 4, p less than 0.02) than the naphthoxylactic acid binding in maternal plasma at delivery (97.6 +/- 0.4%). When the simultaneous concentrations of P and naphthoxylactic acid in maternal and cord plasma are compared in conjunction with protein binding and ionic effects, it would seem that metabolism of P does occur in the placental/foetal unit.

Blood Proteins↗
PubMed1983

Apple II program to simulate the response-time profile of non-depolarising muscle relaxants.

We have developed a BASIC program for the Apple II microcomputer which can simulate the effect (degree of paralysis) time curve obtained following bolus intravenous administrations of pancuronium. The program is based on a combined pharmacokinetic/pharmacodynamic model and has practical application to the anaesthetist under operating room conditions. Knowing the disease state of the patient and the doses and times of administration of pancuronium the microcomputer can predict the degree of paralysis which exists at any time and so assists in the timing of the next dose of relaxant and in deciding when to effect reversal.

Computers↗
PubMed1983

Propranolol, propranolol glucuronide, and naphthoxylactic acid in breast milk and plasma.

High-performance liquid chromatographic assays for propranolol and its major metabolites in plasma and breast milk are described. The breast milk/whole plasma ratios of propranolol in three lactating women were in the range of 0.33 to 1.65. The half-life of elimination of propranolol from breast milk was 6.5 +/- 3.4 h (mean +/- SD), which was significantly longer (t = 1.844, df = 4, p less than 0.01) than the half-life of elimination of propranolol from plasma, which was 2.6 +/- 1.2 h (mean +/- SD). The half-life of elimination of the propranolol metabolite naphthoxylactic acid from breast milk was 4.2 +/- 0.9 h (mean +/- SD), which was not significantly different (t = 0.042, df = 4, p greater than 0.05) from the mean half-life of elimination from plasma, which was 4.2 +/- 1.2 h (mean +/- SD). The penetration of propranolol glucuronide into breast milk was slower and to a lesser extent than that of propranolol and naphthoxylactic acid. The maximum dose, calculated from the results presented in this paper, ingested as either propranolol or as propranolol glucuronide in breast milk by the neonate would be less than 0.1% of the maternal dose.

Female↗
PubMed1983

Determination of nitrazepam and temazepam in plasma by high-performance liquid chromatography.

A rapid and simple high-performance liquid chromatographic analysis of nitrazepam in plasma with temazepam as an internal standard is described here. Alternatively, this assay method can also be used to determine temazepam plasma concentrations with nitrazepam as the internal standard. Chloroform was used as an organic solvent for the extraction process. The percentage recoveries of nitrazepam and temazepam were 79% and 85%, respectively. The coefficient of variation of the within-day precision of the assay procedure at a concentration equal to 50 ng/ml of nitrazepam was 2.4% (n = 5), and that for day-to-day precision at the same concentration was 4.7% (n = 5). Calibration curves for nitrazepam and temazepam were linear over their therapeutic ranges. Pharmacokinetic parameters obtained with this method after a single oral dose of 5 mg of nitrazepam in five normal subjects were comparable to results obtained in previous studies.

Anti-Anxiety Agents↗
PubMed1981

Dose-response curves for four neuromuscular blockers using continuous i.v. infusion.

Cumulative dose-response curves were constructed in man for tubocurarine, pancuronium, gallamine and alcuronium from data obtained during barbiturate-narcotic-nitrous oxide anaesthesia. Fifty-six adult patients received one of these drugs, administered by constant-rate infusion, a technique enabling response levels and results pooled to derive a composite dose-response curve for each drug. Using the mechanical twitch response, the ED50 for each neuromuscular blocking drug was: tubocurarine 0.236 mg kg-1, pancuronium 0.048 mg kg-1, gallamine 1.3 mg kg-1 and alcuronium 0.161 mg kg-1. The slopes of the composite curves for pancuronium and alcuronium were significantly steeper than those for tubocurarine and gallamine. In the alcuronium studies the simultaneous compound electromyogram was recorded, and usually this was more depressed than the mechanical twitch response, giving an ED50 of 0.135 mg kg-1.

Action Potentials↗
PubMed1981

Gallamine disposition in surgical patients with chronic renal failure.

1 Plasma levels of gallamine and the elicited neuromuscular response have been measured in seven patients with compromised renal function who received a single 2 mg/kg dose and in a further patient who received an initial dose of 2 mg/kg followed by two additional doses of 1 mg/kg. 2 The plasma level-time data from all patients was adequately explained by a biexponential equation interpreted as a two-compartment open mammillary model. 3 Comparison of the model-independent pharmacokinetic parameters for gallamine between these patients and a group of normal patients revealed that the elimination phase half-life (T and one-half beta) was significantly prolonged in renal failure with a marked reduction in the plasma clearance of gallamine. 4 Gallamine had larger apparent volumes of distribution in the presence of renal failure than those found in normal patients. 5 The peak paralysis levels attained and the associated plasma concentrations of gallamine were similar in patients with and without renal failure. 6 At this low dosage the rate of recovery from paralysis in renal failure patients, though similar to that noted normally, appeared to be somewhat slower in some patients. 7. The results suggest that gallamine is not to be preferred to other nondepolarizing muscle relaxants in patients with renal failure.

Adult↗
PubMed1981

Gastric emptying rate in the elderly: implications for drug therapy.

The effect of the aging process on gastric emptying was studied in 11 elderly subjects (mean age, 77) and in 7 young healthy volunteers (mean age, 26). Gastric emptying rates were assessed by a modified sequential scinti-scanning technique after administration of the nonabsorbable chelated radiopharmaceutical 99mTc-DTPA. The rate of emptying, expressed as half-time (T 1/2e) in minutes, was significantly longer (p less than 0.001) in the elderly subjects (mean apparent T 1/2e = 123.23 min) compared to the young healthy volunteers (mean apparent T 1/2e = 49.69 min). Clinical implications of these findings are discussed, particularly with respect to the rate and extent of drug absorption in elderly persons.

Administration, Oral↗