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Biomedical subjects

T A Moreland

Publications and source records attributed to T A Moreland.

At least 19 recordsLinked to original sources
PubMed2001

Test-retest reliability of the ulnar F-wave minimum latency versus ulnar distal motor latency in healthy adults.

BACKGROUND AND PURPOSE: The purposes of this study were to explore reliability of the ulnar F-wave minimum latency (Fmin) and the ulnar distal motor latency (DML) and to contrast those levels of reliability in order to reveal whether physiologic lability is the primary contributor to unwanted variability in Fmin measurements. SUBJECTS AND METHODS: Fmin and DML in the Abductor Digiti Minimi muscle were measured bilaterally by two raters in 50 healthy adults (n = 100 hands, 70 male, 30 female) with 3-14 days between testing sessions. RESULTS: Intrarater reliability (ICC 3,1) for the Fmin was 0.89 with a standard error of the measurement (SEM) of 0.77 msec. Interrater reliability (ICC 2,1) for the Fmin was 0.80 with a SEM of 1.04 msec. Intrarater reliability (ICC 3,1) for the DML was 0.71 with a SEM of 0.18 msec. Interrater reliability (ICC 2,1) for the DML was 0.76 with a SEM of 0.19 msec. DISCUSSION AND CONCLUSIONS: Contrary to our hypothesis, the Fmin had a higher reliability than the DML. The DML did not display the high reliability other investigators have reported. We conclude the Fmin is a reliable measurement when 10 supramaximal stimulations are administered to healthy, young to middle-aged adult subjects. However, no inferences were made regarding relative levels of psychologic lability for the two latencies.

Adult↗
PubMed1999

[A relative bioavailability study of 2 oral formulations of omeprazole after their administration in repeated doses to healthy volunteers].

To determine the relative bioavailability of Ulceral (study formula) with respect to Losec (reference standard formula) and establish their bioequivalence daily doses of 20 mg of omeprazole were given during 5 consecutive days to 24 healthy volunteers. No significant differences were observed in the area under the curve (AUC0-t), a parameter directly related to the inhibition of acid secretion induced by omeprazole. The confidence interval of 90% for the difference between the two formulations for AUC0-t was within the interval of acceptance (0.80-1.25). The confidence interval for the difference between the two formulations for Cmax were also within the range of acceptance (0.70-1.43). In relation to the time for achieving (Cmax (tmax), the difference between the two formulations and the confidence interval of 95% for the tmax was 0.75 (-0.5-1.75) h indicating that no significant differences were observed between the two treatments. This study confirms the bioequivalence of Ulceral with the standard reference formulation as well as the tolerability of the two formulae.

Administration, Oral↗
PubMed1992

Ethanol kinetics: extent of error in back extrapolation procedures.

1. Plasma ethanol concentrations were measured in 24 male volunteers for 9 h after a single oral dose of 710 mg kg-1. 2. The rate of decline of the plasma ethanol concentration (k0; mean +/- s.d.), was 186 +/- 26 mg l-1 h-1. 3. In each individual, three elimination rates were used to back-extrapolate plasma ethanol concentrations over 3 and 5 h periods from observed values at 4 h and 6 h post-dosing assuming zero-order kinetics. The extrapolated values were then compared with the observed concentrations. 4. Using the mean k0 values for the subjects the mean error in back extrapolation was small but highly variable. The variability in the error increased with the length of the extrapolation period. 5. When a k0 value of 150 mg l-1 h-1 (a value often cited as a population mean) was used for back extrapolation this resulted in significant under-estimation of actual values whereas the use of a k0 value of 238 mg l-1 h-1 (the highest value observed in the present study) resulted in significant over-estimation of actual values. 6. These results indicate that because the kinetics of ethanol are associated with substantial inter-subject variability the use of a single slope value to back calculate blood concentrations can give rise to considerable error.

Adult↗
PubMed1991

Relationship between cefpirome clearance, serum creatinine, weight and age in patients treated for infection.

Cefpirome serum concentrations were measured by microbiological assay in 30 patients after five to nine days of treatment with 1 or 2 g bd for moderate to severe infection of presumed bacterial origin. Patients with serum creatinine (SCr) greater than 220 mumol/L were excluded. The age of patients ranged from 34-86 years. Creatinine clearance (Clcr) was calculated from age, sex, weight and SCr. The range of SCr was 63-220 mumol/L and the range of Clcr was 18-169 mL/min. The correlation coefficient with cefpirome clearance was 0.464 for SCr and 0.747 for Clcr. More than half of the patients with Clcr less than 50 mL/min had SCr within the normal range of 70-150 mumol/L. Mean cefpirome clearance in patients with Clcr 18-50 mL/min was 42.7 mL/min, which is very similar to the figure of 43.5 mL/min reported in a single dose volunteer study in patients with renal failure. Mean cefpirome clearance in patients with Clcr greater than 80 mL/min was 107.6 mL/min. In conclusion, these data on cefpirome clearance obtained after multiple dose treatment of patients with presumed bacterial infection are consistent with data previously obtained from single dose volunteer studies and support the currently recommended dose regimens. Clinicians should take account of age, weight and sex when estimating renal function from SCr.

Adult↗
PubMed1990

Bioavailability of cefuroxime axetil: comparison of standard and abbreviated methods.

A randomized cross-over study comparing serum and urinary concentrations of cefuroxime after a 750 mg intravenous dose of cefuroxime and a 500 mg oral dose of cefuroxime axetil was conducted to evaluate the bioavailability of the current marketed formulation of cefuroxime axetil. The absolute bioavailability was compared with various abbreviated methods of assessing bioavailability. The peak concentrations (Cmax) and times to peak (Tmax) varied considerably (range 4.7-12.0 mg/l and 1.5-4 h respectively). The absolute bioavailability was 67.9%. The urine recovery after oral dosage and urine bioavailability were 38.6% and 50.3% respectively. The mean AUC0-6 h after the oral dosage was 27.7 mg/l.h. Both urine recovery and urine bioavailability were poor indicators of bioavailability (r = 0.54, r = 0.33 respectively). Although AUC0-6 h after the oral dose was positively correlated with absolute bioavailability, the coefficient of determination (r2) indicated that only 56% of the variation in absolute bioavailability was explained by AUC0-6 h. This study demonstrated that the current formulation of cefuroxime axetil is reliably absorbed although there is considerable variation in Cmax and Tmax. Because of this variation and because the abbreviated methods were unsatisfactory, we recommend that bioavailability of cefuroxime axetil in patients should be measured by formal intravenous/oral cross-over serum concentration studies.

Biological Availability↗
PubMed1989

Pharmacokinetics, efficacy and adverse effects of sublingual salbutamol in patients with asthma.

Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 micrograms (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggest that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.

Administration, Inhalation↗
PubMed1989

Sustained-release verapamil: multiple-dose pharmacokinetic comparison of 120-mg and 240-mg tablets and the effect of halving a 240-mg tablet.

Ten healthy male volunteers, aged 18-37 years, entered a balanced crossover comparison of the pharmacokinetic profiles of (a) one 240 mg verapamil HCl sustained-release tablet (Isoptin SR 240, Securon SR) (1 X 240 mg) and (b) either: two half 240-mg verapamil HCl sustained-release tablets (2 X half 240-mg tablets, Study 1) or two 120-mg verapamil HCl sustained-release tablets (Isoptin SR 120) (2 X 120 mg, Study 2). Each phase of the two studies consisted of once-daily administration of verapamil for 8 days with a 1-week washout period between phases. Plasma samples were collected for 24 h after dosing on day 8 of each phase and assayed for verapamil and norverapamil by high-performance liquid chromatography. In both studies there were no significant differences between the mean Cmax, Tmax, and area under curve values observed after the two treatments. There were no significant differences between mean verapamil plasma concentrations at any time during the dose interval. The mean bioavailability of the 120-mg tablet relative to the 240-mg tablet was 107%, with 95% confidence limits of 81 and 142%, indicating that the amount of verapamil available from the two tablets was similar. This investigation indicates that both tablet sizes appear to have similar sustained-release properties and that the formulation retains its sustained-release properties when the tablet is broken.

Adolescent↗
PubMed1988

A comparison of digoxin, diltiazem and their combination in the treatment of atrial fibrillation.

Fourteen patients (four females) with chronic atrial fibrillation were entered into a randomized, double-blind crossover study to compare the effects of treatment with diltiazem alone, digoxin alone, and a combination of diltiazem plus digoxin. The dose of digoxin was adjusted so as to achieve serum concentrations within the range 1.3-2.6 nmol l-1 between six and eight hours after dosing. Four patients were withdrawn from the study; three patients experienced side effects while taking diltiazem and one reverted to sinus rhythm while taking digoxin. Among the remaining 10 patients, mean heart rates were significantly lower during treatment with the combination of digoxin and diltiazem than with digoxin alone both at rest, after exercise and during ambulatory ECG monitoring. Post-exercise heart rates were reduced by 15% with combination therapy when compared with digoxin alone (151.9 vs. 128.1 bpm), but there was no evidence that this reduction in ventricular rate was associated with improved exercise tolerance. The results suggest that further reduction of the rapid ventricular rates seen in digitalized patients with AF by the use of diltiazem does not appear to be of benefit in the majority of patients.

Aged↗
PubMed1988

Improvement in morning hyperglycaemia with basal human ultratard and prandial human actrapid insulin--a comparison of multiple injection regimens.

Three 'pen'-administered multiple injection regimens have been compared with twice daily insulin injection regimens by means of 24-h profiles of plasma glucose and free insulin concentrations. Ten Type 1 diabetic patients received their usual twice daily insulin regimen and were then randomized to receive the same total daily insulin dose in four divided doses using (1) 50:50 premixed soluble and isophane, (2) 30:70 premixed soluble and isophane, and (3) preprandial soluble and evening crystalline-zinc insulins. Profiles were performed after 1 week on each regimen. Plasma glucose concentrations were similar during the twice daily regimen and the two premixed regimens, rising during the early hours of the morning to a peak between 0900 and 0930 h of 13.8 +/- 2.8 (+/- SD) mmol l-1 on the twice daily regimen, 13.6 +/- 5.3 mmol l-1 on the premixed 50:50 regimen, and 13.5 +/- 4.2 mmol-1 on the premixed 30:70 regimen. With the basal and prandial regimen, overnight plasma glucose concentrations were higher than with the other regimens between 2400 and 0300 h (p less than 0.05). Concentrations then fell until breakfast, and rose after this meal to a peak of 9.5 +/- 4.3 mmol l-1 (p less than 0.01). Mean plasma glucose concentrations were significantly lower than on the other three regimens between 0830 and 1100 h (p less than 0.05). Less variability was observed in 24-h mean plasma glucose concentrations during the basal and prandial regimen than during the other three regimens.

Adult↗
PubMed1987

Ciprofloxacin in plasma and peritoneal dialysate after oral therapy in patients on continuous ambulatory peritoneal dialysis.

The quinolone antibiotic ciprofloxacin offers the possibility of effective oral treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) if a sufficiently high concentration is attained in peritoneal dialysate. The pharmacokinetics of oral ciprofloxacin have been studied in ten CAPD patients given 250 mg qds for two days. Five patients were being treated for peritonitis with gentamicin and cefuroxime; the remaining five were receiving inpatient training for CAPD or were being treated for other problems. Ciprofloxacin concentration in plasma and in dialysate were determined by HPLC. There were not differences in plasma and dialysate kinetics in patients with and without peritonitis. Plasma levels were higher and the elimination half-life was longer than those reported for healthy subjects. Dialysate and plasma levels were significantly correlated (r2 = 0.87, P = 0.001), with dialysate levels consistently lower than plasma levels. Dialysate levels exceeded 1 mg/l in seven patients. The mean peak dialysate level (2.17 +/- 1.63 mg/l) exceeded the MIC of ciprofloxacin for 32 of 34 bacterial strains responsible for peritonitis. Ciprofloxacin shows promise as a useful oral treatment of CAPD-associated peritonitis.

Administration, Oral↗
PubMed1987

A comparison of verapamil and digoxin in the treatment of atrial fibrillation.

Twelve patients (including 2 females) with chronic atrial fibrillation were entered into a randomized, double blind crossover study to compare the effects of digoxin and verapamil upon heart rate, exercise tolerance and symptom control. The dose of digoxin was adjusted so as to give serum concentrations within the range 1.3 to 2.6 nmol l-1 between four and six hours after dosing, and was continued for six weeks. The dose of verapamil was increased from 40 mg tds to 80 mg tds to 120 mg tds at fortnightly intervals. Three patients did not complete the study; two because of adverse effects attributable to verapamil. In the remaining nine patients, mean post exercise heart rates were significantly lower during treatment with verapamil 80 mgs tds (126.7 bpm) than with verapamil 40 mg tds (148.6 bpm) or digoxin (146.7 bpm). However, exercise tolerance was similar with both verapamil and digoxin and the superior control of exercise induced tachycardia achieved with higher doses of verapamil was not associated with improved exercise endurance. Visual analogue scale scores for constipation were significantly higher during treatment with verapamil; scores for other possible side effects and for overall wellbeing were similar. The results do not confirm the findings of others who have reported that verapamil is superior to digoxin in the treatment of atrial fibrillation.

Aged↗
PubMed1984

Stiripentol kinetics in epilepsy: nonlinearity and interactions.

Stiripentol kinetics during oral therapy were assessed in six patients with epilepsy who were receiving other antiepileptic drugs. Steady-state levels at 600, 1200, and 2400 mg/day increased in a nonlinear fashion, indicating Michaelis-Menten kinetics. Oral clearance of stiripentol at 600 mg/day was 41.5 +/- 23.4 l/day/kg (mean +/- SD), greater than that at 1200 mg/day (20.3 +/- 8.8 l/day/kg; P less than 0.05) or 2400 mg/day (8.5 +/- 3.8 l/day/kg; P less than 0.01). The apparent in vivo Michaelis-Menten parameters were determined from three mean steady-state concentrations. The average velocity of conversion of stiripentol to its metabolites (Vm), Michaelis constant (Km), and the ratio Vm/Km were 49.3 +/- 13.1 mg/day/kg, 1.35 +/- 1.08 mg/l, and 50.2 +/- 27.5 l/day/kg. Stiripentol reduced the elimination clearances of concomitant antiepileptic drugs. Phenytoin clearance was reduced in all five subjects who received this drug, from a mean control of 29.5 +/- 13.4 l/day to 18.5 +/- 4.6 l/day at a stiripentol dose of 1200 mg/day (P = 0.05) and to 6.48 +/- 2.59 l/day at 2400 mg/day (P less than 0.01). Stiripentol reduced the clearance of carbamazepine in one subject from a control value of 209 l/day to 128 l/day (1200 mg/day) and 61 l/day (2400 mg/day). Stiripentol reduced phenobarbital clearance in two subjects from 3.8 and 5.1 l/day to 2.3 and 3.4 l/day (2400 mg/day). The Michaelis-Menten kinetics of stiripentol, as well as its interactions with other antiepileptic drugs, have important implications in the designing of controlled clinical trials.

Administration, Oral↗
PubMed1984

Michaelis-Menten kinetics of stiripentol in normal humans.

Michaelis-Menten kinetic parameters for stiripentol, and anticonvulsant, were assessed in six normal volunteers. Stiripentol was administered orally three times a day in dosage increments of 600, 1,200, and 1,800 mg/day for consecutive periods of 3, 4, and 7 days, respectively. Stiripentol steady-state levels at the three dosing rates increased more than proportionally with dose. The mean +/- SD oral clearance of stiripentol at 600 mg/day (1,090 +/- 624 L/day) was significantly greater (p less than 0.01) than at 1,200 (506 +/- 219 L/day) or 1,800 (405 +/- 151 L/day) mg/day. Average steady-state concentrations predicted from individually determined Vm and Km parameters were in good agreement with experimentally observed levels, indicating that the kinetics of stiripentol are of the Michaelis-Menten type. The mean Vm, Km, and Vm/Km ratio were 2,299 +/- 490 mg/day, 2.20 +/- 1.28 mg/L, and 1,241 +/- 837 L/day, respectively. Neuropsychological tests carried out before and after 14 days of stiripentol treatment showed a significant decline in verbal learning ability (p = 0.038) and a significant improvement in a test of memory and attention (p less than 0.01).

Adult↗
PubMed1984

Carbamazepine/valproic acid interaction in man and rhesus monkey.

Sodium valproate (VPA) was administered for 1 week (1 g b.i.d.) to seven epileptic patients receiving chronic carbamazepine (CBZ) therapy. Steady-state CBZ levels determined before and after VPA therapy were reduced by 3-59% in six patients and were unchanged in one patient. The plasma concentration ratio of carbamazepine-10,11-epoxide ( CBZE ) to CBZ increased in all patients by 11-500%. The plasma binding of CBZ was determined in six healthy volunteers given a single 400 mg CBZ dose with and without the coadministration of 1 g VPA in a cross-over design. The mean CBZ free-fraction was increased in three of the subjects (p = 0.008-0.031), decreased in one subject (p less than 0.002), and remained unchanged in two subjects when VPA was administered. Four male rhesus monkeys were infused intravenously with CBZ (15 mg h-1) for 5 days and then three consecutive 24-h infusions were given: I, CBZ alone; II, CBZ with 75 mg h-1 VPA; III, CBZ with 150 mg h-1 VPA. The mean free-fraction of CBZ and CBZE increased during infusions II and III from 31.5 +/- 2.7% to 33.6 +/- 2.6% (p less than 0.05) and 37.7 +/- 1.3% (p less than 0.01) for CBZ and from 46.9 +/- 9.2% to 53.6 +/- 5.7% (p greater than 0.05) and 60.1 +/- 4.0% (p less than 0.01) for CBZE . The clearance of free CBZ declined from 7.96 +/- 1.75 to 4.84 +/- 1.26 (p less than 0.01) and 4.12 +/- 1.75 (p less than 0.01) 1 kg-1h-1 during infusions II and III, respectively. The mean free CBZE /CBZ ratio increased from 0.12 +/- 0.03 to 0.24 +/- 0.03 and 0.36 +/- 0.04 during infusions II and III, respectively (p less than 0.001). These findings indicate a decrease in the elimination clearance of CBZE possibly coupled with a decrease in its formation clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Rationale for monitoring free drug levels.

Recent developments in our knowledge of drug binding prompt the questions, in what circumstances are measurements of free levels necessary, desirable or not warranted? Free level monitoring should be considered for drugs for which the usefulness of plasma level monitoring has been established, drugs which are highly bound to plasma proteins, and which exhibit a variable free fraction. In terms of drug distribution, free drug concentration is independent of free fraction, while total concentration is a resultant of free concentration and free fraction. For drugs with a low extraction ratio, the total concentration at steady-state depends upon free fraction, but the free concentration is independent of free fraction. With high extraction ratio drugs, the free concentration is dependent upon free fraction but only after parenteral administration. There are numerous examples of drugs which are highly bound and exhibit large variations in free fraction. Free fraction may increase with drug concentration. Pathophysiological changes in the binding ligands, albumin and alpha 1-acid glycoprotein, as well as changes in the concentration of endogenous compounds which compete for binding sites, may also cause changes in free drug fraction. Binding interactions resulting from polytherapy may also result in a variable free fraction. Ultrafiltration devices now enable the convenient and accurate determination of free drug levels. Areas in which this should prove useful are investigations of concentration-effect relationships and clinical situations requiring intensive monitoring where binding changes are suspected.

Aged↗