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Biomedical subjects

S Loft

Publications and source records attributed to S Loft.

52 records · Page 3Linked to original sources
PubMed1987

Influence of prednisolone on antipyrine elimination in patients with obstructive lung disease.

The influence of prednisolone on the elimination of antipyrine has been investigated. The one-sample antipyrine clearance was estimated in 23 outpatients with obstructive lung disease before and after treatment with prednisolone 30 or 50 mg/day for 7 days. During prednisolone administration antipyrine clearance decreased from 54.9 +/- 14.8 to 51.7 +/- 14.6 ml/min (mean +/- SD; p less than 0.05). The results indicate that prednisolone decreases the rate of antipyrine elimination, but not to an extent suggesting a clinically important change in hepatic drug metabolism.

Antipyrine↗
PubMed1987

Metronidazole pharmacokinetics in patients with hepatic encephalopathy.

The pharmacokinetics of metronidazole and its major metabolites was investigated in eight patients with liver cirrhosis and coma of grade 2 to 4 and in eight healthy controls. In the coma patients the systemic clearance of metronidazole was reduced (29 +/- 10 versus 83 +/- 14 ml/min, mean +/- SD; p less than 0.001) and the elimination half-life prolonged (20 +/- 9 versus 7.3 +/- 0.9 h; p less than 0.001), whereas the volume of distribution at steady state was unchanged (44 +/- 9 versus 48 +/- 7 l) as compared with the healthy controls. Investigation of the major elimination pathways of metronidazole showed that the decreased rate of elimination in the patients was mainly due to impaired hepatic drug oxidation. In four patients therapeutic plasma concentrations were achieved during 6 days' treatment with 500 mg metronidazole per 24 or 48 h.

Aged↗
PubMed1987

Increased susceptibility to liver disease in relation to alcohol consumption in women.

Sex-related differences were prospectively studied in patients with the first presentation of alcoholic liver disease. Among 42 patients the diagnosis was cirrhosis in 8 women and 15 men, alcoholic hepatitis in 4 women and 1 man, steatosis in 6 women and 6 men, and no histologic changes were found in the liver biopsy specimens from 2 men (p greater than 0.1). The median (range) antipyrine clearance was 14.6 (1.0-64) versus 17.2 (3.0-83) ml/min and the clinical score in accordance with the Pugh modification of the Child-Turcotte classification was 8 (5-13) versus 8 (5-11) in the women and men, respectively (p greater than 0.05). In 5 women and only 1 man the antipyrine clearance was less than 5 ml/min, indicating an almost total loss of functional liver mass (p less than 0.05), whereas the Pugh score was above 11 in 6 women, but not in any of the men (p less than 0.05). On an average, the men estimated their total lifetime consumption of alcohol to be 2.1 times greater and the number of days they had consumed more than 5 drinks 2.9 times higher than the women (p less than 0.05). These ratios are reduced to 1.4 and 1.7, respectively (p greater than 0.05), if the female alcohol intake is adjusted to the average male volume of distribution. The results support the concept that women may develop similar, and sometimes even more severe, liver disease after consumption of less alcohol than men. The apparent difference in susceptibility to alcohol may be partly explained by differences in volume of distribution.

Adult↗
PubMed1987

Effect of concomitant administration of cimetidine and phenobarbital on antipyrine elimination and metabolite formation.

Cimetidine 1000 mg/day and phenobarbital 100 mg/day were given to five healthy volunteers for 13 days in order to investigate the combined effect and time course of inhibition and induction on hepatic drug metabolism. The one-sample antipyrine saliva clearance (APC) and urinary metabolite profile were measured weekly, once before, two times during and four times after drug administration. On the second day of drug treatment APC was 0.7 fold and the formation clearance of the 3 oxidized metabolites 0.6 fold decreased owing to an early inhibition by cimetidine (p less than 0.05). After 8 days of concomitant drug administration, i.e. when the drug mediated inhibition and induction are supposed to be at maximum, mean APC was 0.85 times the initial value (p greater than 0.05), whereas the formation clearances of nor- and 3-hydroxymethylantipyrine were still significantly depressed. Four and 11 days after drug withdrawal, when phenobarbital, but not cimetidine could be demonstrated in plasma, APC was 1.2 times the initial value (p less than 0.05). The results suggest, that the respective effects of cimetidine and phenobarbital on antipyrine elimination are additive, when given concomitantly, but that cimetidine exerts a relatively greater inhibition in the phenobarbital induced state.

Adult↗
PubMed1986

Influence of dose and route of administration on disposition of metronidazole and its major metabolites.

The influence of dose and route of administration on the kinetics of metronidazole and its major metabolites has been investigated in 8 healthy volunteers given 0.5 and 2.0 g i.v. and p.o. Metronidazole elimination kinetics from plasma could be described by an open two-compartment model. The systemic oral bioavailability of both doses was approximately 1. The total systemic clearance of the intravenous 2.0 g dose was 9% lower than that of the 0.5 g dose (p less than 0.05). There were no significant dose-related differences in volume or rate of distribution. The elimination half-life was similar after the four treatments with metronidazole. The major elimination pathways, renal excretion and hepatic oxidation and glucuronidation, accounted for more than 2/3 of the total systemic clearance. Clearance both by hepatic oxidative metabolism and renal excretion was significantly lower after 2.0 than after 0.5 g i.v., whereas there was no significant difference after the oral doses. The results indicate that a high therapeutic dose of metronidazole may be eliminated at a reduced rate, but this is probably not of clinical importance. No single saturable elimination pathway was identified.

Administration, Oral↗
PubMed1986

Pulmonary disease and antipyrine clearance.

We investigated hepatic microsomal enzyme activity by the one-sample saliva test for antipyrine clearance determination in 35 homozygous, alpha 1-antitrypsin-deficient outpatients with chronic pulmonary disease. Twenty-five outpatients with chronic obstructive lung disease and comparable lung function impairment and 31 healthy volunteers served as controls. Antipyrine clearance did not differ significantly between the two groups of patients with pulmonary disease. However, the clearance was 18% lower in these two groups than in the healthy volunteers (P less than 0.01). Antipyrine clearance was lowest in patients with severe lung function impairment (P less than 0.01).

Adult↗
PubMed1986

Increased hepatic microsomal activity after halothane anaesthesia in children.

The effect of anaesthesia and surgery on microsomal enzyme activity was studied in 19 children aged 4-9 years, scheduled for tonsillectomy. The children were randomly allocated to either halothane or ketamine anaesthesia. Antipyrine clearance was measured before and 4 days after surgery by a salivary one-sample technique. Statistically significant (p less than 0.001) increases in antipyrine clearance was found in children who received halothane anaesthesia. The antipyrine clearance was increased by a mean of 26% 4 days after surgery, compared with a pre-operative control measurement. No significant change in antipyrine clearance was observed in children who received ketamine anaesthesia. There was also a significant difference in antipyrine clearance changes after surgery between the two groups (p less than 0.05). Halothane has enzyme-inducing properties after a single exposure in children, while a single dose of ketamine does not.

Anesthesia, Inhalation↗
PubMed1986

Inhibition of antipyrine elimination by disulfiram and cimetidine: the effect of concomitant administration.

We investigated the effect of concomitantly administered disulfiram and cimetidine on antipyrine elimination. On day 1, 2, 4 and 6 of two periods of 6 days one sample antipyrine saliva clearance (APC) was measured in nine healthy volunteers. From day 2 to 6 of period I disulfiram 400 mg day-1 was administered and on day 5 and 6 cimetidine 1000 mg day-1 was added. In period II only cimetidine was given (on days 5 and 6). On day 4 of period II APC was increased 1.3 fold, probably due to self-induction by repeated antipyrine administration. Taking this into account disulfiram and cimetidine separately decreased APC 0.64 and 0.70 times, respectively. When both inhibitors were given APC was reduced 0.52 times. The results suggest that the effects of cimetidine and disulfiram on antipyrine elimination are additive.

Adult↗
PubMed1985

Antipyrine clearance in pneumonia.

Antipyrine clearance was estimated by a one-sample technique in 14 patients with acute fever and clinical pneumonia. Antipyrine clearance during the acute illness was 31.4 +/- 7.6 ml/min (X +/- SD). Fourteen and 28 days later during convalescence, clearance values were higher (47.8 +/- 18.9 and 49.2 +/- 15.0 ml/min, respectively). We conclude that microsomal hepatic drug metabolism in adults is impaired during pneumonia.

Adult↗
PubMed1985

Increased hepatic microsomal enzyme activity after surgery under halothane or spinal anesthesia.

Thirty-two fit patients scheduled for explorative arthrotomy of the knee were allocated randomly to either halothane/oxygen anesthesia or spinal anesthesia with bupivacaine 0.25 mg X kg-1. The day before and 1, 10, and 21 days after surgery, the aminopyrine breath test (ABT) was performed. The day before and 5, 10, and 21 days after surgery, the antipyrine clearance (APcl) was measured by the single sample saliva technique. The ABT as well as the APcl were increased significantly postoperatively (P less than 0.01). The day after surgery the ABT was increased by 13 +/- 21% in the spinal anesthesia group only, whereas a late increase by 14 +/- 31% was found in the halothane group. Five days after surgery, the APcl was increased by 36 +/- 45% in the spinal anesthesia group and by 21 +/- 28% in the halothane group. Both tests returned to base line values within 3 weeks postoperatively. In five volunteers following the same sampling scheme but receiving bupivacaine 0.25 mg X kg-1 im without surgery, no change in the ABT or the APcl was observed. The authors conclude that surgery may cause microsomal enzyme induction regardless of the anesthetic agent or technique used. The mechanism of this induction remains to be elucidated.

Adolescent↗
PubMed1985

Antipyrine clearance in children from single saliva samples.

The saliva clearance of antipyrine was measured in 18 children from four samples taken about 9, 13, 22 and 25 h after ingestion of 20 mg kg-1. Antipyrine clearance determined from each of the samples using a volume of distribution estimated from age (A) and body weight (BW) and height (BH) (V = 1.535 X A + 0.339 X BW + 0.300 X BH - 35.63 (1] correlated closely with clearance determined from the total elimination curve (r greater than 0.94). Random variation and systematic deviation were minimal when the 22 h sample was used for clearance determination (r = 0.98, P less than 0.001, regression curve slope = 1.00, intercept = 0.58 and residual variance = 4.02). The one-sample method for determination of antipyrine saliva clearance is non-invasive, easy to perform and acceptable to children.

Antipyrine↗
PubMed1985

Jet fuel and liver function.

The impact of occupational exposure to jet fuel on antipyrine elimination was studied in 91 fuel-filing attendants. The mean antipyrine clearance was enhanced to 68.4 (SD 19.5) ml/min during exposure to jet fuel compared to 57.9 (SD 18.1) ml/min after an exposure-free period of two to four weeks. The corresponding values for 47 office workers (referents) were 62.7 (SD 22.2) ml/min and 56.4 (SD 22.3) ml/min. The median jet fuel concentration in the breathing zone of the fuel-filling attendants was 31 (range 1-1 020) mg/m3. No known inducing factor could be identified in the work environment of the office workers. No difference in the concentration of aspartate aminotransferase and alkaline phosphatase in serum was found either within or between the groups. Our study indicates that jet fuel, which is a mixture of aliphatic and aromatic organic solvents resembling gasoline and white spirit, is an inducer of hepatic drug metabolism in man.

Aerospace Medicine↗
PubMed1983

Influence of moderate alcohol intake on wakening plasma thiopental concentration.

In an earlier study, an inverse correlation between thiopental-induced sleeping time and alcohol intake in the preceding week was demonstrated in women undergoing termination of pregnancy. In order to investigate the mechanism behind the apparent cross-tolerance, the relationship between alcohol consumption in the week preceding thiopental/nitrous oxide/oxygen anesthesia and wakening plasma thiopental concentration on one hand and sleeping time on the other was examined in 68 women scheduled for termination of pregnancy and in 37 women scheduled for diagnostic uterine dilatation and curettage. In terms of pure alcohol, the weekly intake (mean +/- s.d.) was 1.17 +/- 2.07 ml . kg-1 in the former and 1.49 +/- 1.70 ml . kg-1 in the latter group. A positive correlation between alcohol consumption and wakening plasma thiopental concentration was found in both groups, reaching statistical significance (P less than 0.05) in the group undergoing termination of pregnancy, but not in the other. The inverse correlation found earlier between alcohol intake and sleeping time was not reproduced significantly in any of the groups. The results indicate that moderate alcohol intake may induce cerebral tolerance to thiopental.

Abortion, Induced↗
PubMed1982

Influence of moderate alcohol intake on thiopental anesthesia.

The relationship between alcohol intake over the week preceding anesthesia and various anesthetic parameters was examined in 119 women scheduled for termination of pregnancy under thiopental-nitrous oxide anesthesia. In terms of pure alcohol, the weekly intake was 1.03 +/- 1.09 ml.kg-1 (mean +/- s.d.), range 0-5.93, i.e. below average consumption in Denmark. Alcohol intake was negatively correlated with anesthetic sleeping time (P less than 0.01). Time and quality of anesthesia induction and frequency of anesthetic complications were not significantly correlated with the use of alcohol. Preanesthetic anxiety was not significantly correlated with any of the above data. Induction time and postoperative awareness were positively and sleeping time negatively correlated with age (P less than 0.05). The results indicate cross-tolerance between alcohol and thiopental, even when the regular intake of the former is low, and increasing thiopental requirements with increasing age.

Abortion, Induced↗