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Biomedical subjects

K C Lasseter

Publications and source records attributed to K C Lasseter.

At least 55 records · Page 3Linked to original sources
PubMed1984

Pharmacokinetics of guanabenz in patients with impaired liver function.

The disposition of guanabenz, a centrally acting antihypertensive agent, was compared in 10 normotensive patients (eight males and two females) with chronic hepatic disease secondary to alcohol abuse and 10 healthy male volunteers after a 16 mg oral dose. Mean plasma concentrations of guanabenz were higher in patients with liver disease than in healthy subjects at every sampling time through 72 h after drug administration (p less than 0.05). In liver disease patients, the mean oral-dose clearance (2 L/h/kg) and terminal-phase volume of distribution (20 L/kg) were lower (p less than 0.001) than the respective values of 11 L/h/kg and 71 L/kg of healthy volunteers. The mean plasma half-life of patients with liver disease (6.4 h) was not significantly longer than that of healthy subjects (4.3 h). The mean fraction of unbound drug in the plasma was higher (p less than 0.01) in patients with liver disease (12.7%) than in healthy volunteers (10.5%). As guanabenz is eliminated predominantly via hepatic biotransformation and undergoes significant presystemic elimination after oral administration, the changes in guanabenz disposition in liver disease are not unexpected. They may be explained by enhanced oral bioavailability, owing to portosystemic shunting and/or reduced intrinsic clearance, combined with decreased hepatic clearance of guanabenz in liver disease. Individual dosage titration may be required when guanabenz is used for antihypertensive therapy of patients with chronic liver disease.

Adult↗
PubMed1984

Steady-state pharmacokinetics of nitrendipine in hepatic insufficiency.

As a calcium antagonist, nitrendipine will be used in the treatment of various diseases in patients with hepatic insufficiency, and it is important to know if they require modified dosing schedules. In this study, six patients with biopsy-confirmed cirrhosis and six age/sex-matched normal healthy subjects were given 10 mg nitrendipine as a single dose on day 1 and 10 mg nitrendipine every 12 h from day 3 through the first dose on day 8. Blood levels of nitrendipine were determined to confirm the attainment of steady state and evaluate the pharmacokinetics in each group. Nitrendipine concentrations were consistently higher in the hepatic group. On day 1, the maximum concentration (Cmax) in the normals was 4.67 +/- 2.60 ng/ml and in the hepatic patients 16.87 +/- 9.42 ng/ml. On day 8, these values were 8.60 +/- 8.82 ng/ml and 27.37 +/- 8.56 ng/ml, respectively. The time to Cmax was not significantly different in the two groups. The elimination half-life was only slightly prolonged from 15.29 +/- 7.25 h in the normals to 19.57 +/- 4.28 h in the hepatic impairment group. This resulted in a marked increase in the area under the concentration-time curve from 28.71 +/- 28.92 ng . h/ml for the normals to 119.56 +/- 34.39 ng . h/ml for the hepatic patients on day 1 and similar results on day 8. Trough levels at steady state were expectedly higher in the hepatic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Piperacillin kinetics.

Piperacillin was administered to normal, healthy volunteers by an intravenous infusion over 30 min at dosage regimens of 12 gm daily (4 gm every 8 hr) and 24 gm daily (6 gm every 6 hr) for 5 consecutive days. Mean peak serum level after 12 gm daily was 244 +/- 24 (SE) microgram/ml and after 24 gm daily, 353 +/- 7 microgram/ml. After infusion the serum level declined monoexponentially in most subjects. On the 12-gm daily dosage mean values were 60 min for half-life (t1/2), 16 1 for volume of distribution, 188 ml/min for body clearance, and 139 ml/min for renal clearance. The same values on day 4 were 47 min, 12 1, 181 ml/min, and 125 ml/min; the volume of distribution was lower than on day 1. On the 24-gm daily dosage regimen, t1/2 was 60 min; volume of distribution, 16 1; body clearance, 183 ml/min; and renal clearance, 101 ml/min on day 1 compared to 68 min, 15 1, 148 ml/min, and 71 ml/min on day 4, the last 2 being significantly lower than on day 1. High renal clearance values were observed at low serum concentrations and vice versa, suggesting saturation of the tubular secretion process at high piperacillin concentrations in serum.

Adolescent↗
PubMed1976

Nefopam HCl interaction study with eight other drugs.

A controlled clinical trial was undertaken to determine potential for drug interaction of nefopam HCl, a new analgesic, with eight other widely used compounds. Nefopam HCl was administered in combination with these drugs and placebo to forty-five healthy volunteer subjects in nine groups of five subjects each. Possible drug interactions were detected by the occurrence of side-effects and interference with bioavailability of the new analgesic, also by changes in vital signs or in various laboratory tests. Results indicated no statistically significant differences in these parameters between the nefopam HCl-placebo regimen and the other eight combinations. Despite this, there were substantial clinical differences in the intensity and incidence of side-effects with combinations of codeine, pentazocine and propoxyphene. These differences warrant further study. Serum nefopam HCl levels were significantly higher on Day 3 than on Day 1, indicating no defect in bioavailability due to drug interaction. Overall, results of this study support the feasibility of concomitant use of these eight drugs with nefopam HCl for short treatment periods.

Adult↗
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↗
PubMedDate not supplied

Oxaprozin dose proportionality.

Twelve normal subjects each received single 300-, 600-, and 1200-mg oral doses of oxaprozin according to a three-period crossover design. Total drug plasma concentrations did not increase in proportion to the dose administered. Total clearance (CIo) and volume of distribution (Vd) increased with dose, though elimination t1 2 remained unchanged. The fraction of unbound oxaprozin in plasma (fup) varied linearly with total plasma concentration: it increased from 0.068 per cent at 10 micrograms/ml to 0.180 per cent at 170 micrograms/ml. A parameter fup was therefore introduced to express the average degree of unbound drug plasma for a given dose, and to allow the calculation of unbound volume of distribution (Vdu) and intrinsic clearance (CIi) as if binding were constant. Even though fup increased with dose, the overall binding in the body (fub approximately 0.52 per cent) was relatively stable. Neither Vdu nor CIi changed with dose; hence, unbound oxaprozin kinetics can be considered to be linear. Protein binding had no effect on unbound oxaprozin plasma levels within the given dose range, and there was a one-to-one proportionality between the dose administered and the unbound drug concentration in plasma.

Adult↗