[Temperature increases in the classroom and student performance].
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Achievement↗
Biomedical subjects
A Somogyi
Publications and source records attributed to A Somogyi.
Successful substitution of rectal metronidazole administration for intravenous use.
Wound infection and isolation of anaerobic organisms before and after intravenous and rectal administration of metronidazole were studied in 24 505 surgical patients. In the 6303 patients who underwent "risk" surgery (bowel, biliary, gynaecological, or otolaryngological surgery) introduction of intravenous metronidazole was associated with a striking fall in wound infection and wound anaerobe isolation rates; and the changes were maintained when the majority of metronidazole used was in suppository form. In the 18 202 patients who underwent "clean" surgery (e.g., orthopaedic, ophthalmic, and plastic surgery) metronidazole use was associated with a small formulation-independent change in infection rate without change in anaerobe isolation rates. Without compromising clinical care the use of intravenous metronidazole can be limited to a minority of patients with special needs.
Anaerobiosis↗
Disposition and removal of metronidazole in patients undergoing haemodialysis.
The pharmacokinetics and haemodialysis clearance of metronidazole were investigated in four renal failure patients after a single 500 mg intravenous dose and in two renal failure patients on continuous treatment with metronidazole. During dialysis, the volume of distribution of metronidazole was 0.60 +/- 0.04 l/kg, total clearance was 196.0 +/- 60.6 ml/min and the elimination half-life had an harmonic mean of 2.14 h. Extraction across the dialyser was 51.5 +/- 7.8% and was limited to the distribution of drug in plasma water. Dialysis clearance was 125.0 +/- 32.7 ml/min, which represented 62 +/- 6% of total clearance and was 1.75 times the sum of the other clearance mechanisms. The hydroxy metabolite was extracted and cleared by the dialyser to the same degree as metronidazole itself. During the 4 h-dialysis 44.9 +/- 2.6% of the dose was removed by the dialyser in the four patients administered a single dose. Metronidazole is efficiently cleared and extensively removed by dialysis, and therefore dosage adjustments and alterations in the timing of dosage administration are essential in patients undergoing haemodialysis.
Adolescent↗
Cimetidine-procainamide pharmacokinetic interaction in man: evidence of competition for tubular secretion of basic drugs.
The hypothesis that basic drugs can compete for active tubular secretion by the kidney was tested in six healthy volunteers by comparing the single dose pharmacokinetics of oral procainamide before and during a daily dose of cimetidine. The area under the procainamide plasma concentration-time curve was increased by cimetidine by an average of 35% from 27.0 +/- 0.3 micrograms/ml X h to 36.5 +/- 3.4 micrograms/ml X h. The elimination half-life increased from an harmonic mean of 2.92 to 3.68 h. The renal clearance of procainamide was reduced by cimetidine from 347 +/- 46 ml/min to 196 +/- 11 ml/min. All these results were statistically significant (p less than 0.016). The area under the plasma concentration-time curve for n-acetylprocainamide was increased by a mean of 25% by cimetidine due to a significant (p less than 0.016) reduction in renal clearance from 258 +/- 60 ml/min to 197 +/- 59 ml/min. The data suggests that cimetidine inhibits the tubular secretion of both procainamide and n-acetylprocainamide, and, if so, represents the first documented evidence for this type of drug interaction in man. The clinical implications from this study necessitate dosage adjustments of procainamide in patients being concomitantly treated with cimetidine. The interaction is pertinent not only for basic drugs that are cleared by the kidney, but also for metabolites of basic drugs and endogenous substances which require active transport into the lumen of the proximal tubule of the kidney for their elimination.
Absorption↗
Serum lipids during starvation in obesity.
The HDL-cholesterol level was found to decrease during the first week of therapeutic starvation in hyperlipoproteinaemic (hypertriglyceridaemic), diabetic (non-insulin dependent) patients. The possible causes of the finding are discussed, and the view is expressed that the fall in HDL given no cause for discontinuing the caloric restriction or starvation as the therapeutic measures in obesity.
Adult↗
Cimetidine reduces procainamide elimination.
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Acecainide↗
[Ultrasonic examination in the diagnosis of acute pancreatitis].
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Acute Disease↗
Prediction of bioavailability for drugs with a high first-pass effect using oral clearance data.
For drugs with a high hepatic clearance, bioavailability is low due to the so-called "first pass effect". Prediction of the bioavailability for these drugs has been only loosely tested. It is proposed that by plotting the reciprocal of bioavailability versus the oral clearance, a straight line with intercept of unity and slope of reciprocal of hepatic blood flow should ensue. For lignocaine and verapamil, this relationship was found to be strong and gave good predictability, whereas for propranolol this relationship was weak and gave poor predictability. The proposed method may be of value in determining whether the low bioavailability of a drug is due to hepatic first pass metabolism.
Administration, Oral↗
Altered disposition and availability of cimetidine in liver cirrhotic patients.
1 The pharmacokinetics and bioavailability of cimetidine were studied after 200 mg oral and intravenous doses in 14 patients with liver cirrhosis, and results were compared to a control group of 12 ulcer patients. 2 In cirrhotic patients, the volume of the central compartment (0.41 +/- 0.06 v 0.19 +/- 0.09 1/kg) and the volume of distribution at steady-state (1.02 +/- 0.17 v 0.80 +/- 0.24 1/kg) were significantly increased. No differences were observed in the area volume of distribution, the total systemic plasma clearance and renal clearance. The non-renal clearance was significantly decreased from 191 +/- 46 to 123 +/- 102 ml/min. 3 The bioavailability of cimetidine (area method) was significantly increased from 60 +/- 23% to 77 /+- 18% in the cirrhotic patients. Also increased was the time during which plasma levels exceeded 0.5 microgram/ml. 4 Urinary excretion of cimetidine was increased in liver cirrhosis by 32% after intravenous and by 36% after oral administration, while the amount of the sulphoxide metabolite decreased accordingly. Creatinine clearance in the cirrhotic patients was highly correlated with the renal clearance of cimetidine as well as its total plasma clearance.
Adult↗
[Angioneurotic edema and hypocomplementemia in patients with thyroid cancer].
The combination with a malignant tumour of angioneurotic oedema (ANO) elicited by a disturbance of the complement system was studied. After surgical removal of the tumour the pathologic complement component level may become normal and the angioneurotic oedema may disappear. In the reported case an angioneurotic oedema, the disturbance of the complement component and scintigraphic deviations of the thyroid suggested the presence of a thyroid carcinoma. After thyroidectomy the ANO disappeared and the complement component returned to normal. This case draws attention to the possibility that, beside lymphoproliferative and autoimmune diseases and cancer of the rectum, carcinoma of the thyroid may also be in the background of angioneurotic oedema.
Adenocarcinoma↗
Pharmacokinetics and metabolism of antipyrine (phenazone) after intravenous and oral administration.
To 12 healthy male volunteers, 6 smokers and 6 non-smokers, 10 mg/kg antipyrine (phenazone) was administered i.v. and p.o. in random order. Following i.v. administration, antipyrine kinetics could be described best by an open two-compartment model. Absolute bioavailability of an aqueous solution of antipyrine was on average 97%. Antipyrine half-life in smokers was significantly shorter (mean 9.7 h) as compared to non-smokers (mean 11.7 h). Smokers excreted significantly more 3-hydroxymethyl-antipyrine (17.2 +/- 2.4 vs. 14.2 +/- 1.9%) than non-smokers, and clearance to this metabolite was significantly increased in smokers. In addition, cumulative urinary excretion of 4-hydroxy-antipyrine, norantipyrine and 3-hydroxymethyl-antipyrine was on average higher in smokers (77.1 +/- 5.0%) as compared to non-smokers (69.5 +/- 10.8%). Thus, 3-hydroxymethyl-antipyrine formation is induced in smokers.
Administration, Oral↗
Rectal administration of metronidazole provides therapeutic plasma levels in postoperative patients.
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Abdomen↗
Influence of phenobarbital treatment on cimetidine kinetics.
The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase of nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P less than 0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P less than 0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.
Adult↗
Impaired cimetidine absorption due to antacids and metoclopramide.
In 8 healthy subjects the absorption of cimetidine was investigated when given alone, together with 60 ml aluminium/magnesium hydroxide containing antacid (neutralising capacity 26 mmol HCl/10 ml), and together with liquid metoclopramide 14 mg. The antacid significantly (P less than 0.01) reduced the bioavailability (area under the plasma level-time curve) of cimetidine, on average by one third. Metoclopramide also reduced the bioavailability by an average of 22%. The reductions were associated with significantly reduced excretion of cimetidine in urine. There was no change in the half-life or renal clearance of cimetidine, supporting the hypothesis of reduced gastrointestinal absorption. The results indicate that cimetidine and antacids should not be given together, and that the dose of cimetidine may have to be increased if it is administered concomitantly with metoclopramide.
Adult↗
Superiority of stable isotope techniques in the assessment of the bioavailability of drugs undergoing extensive first pass elimination. Studies of the relative bioavailability of verapamil tablets.
Although the absorption of verapamil is almost complete after oral administration, its bioavailability is low due to extensive hepatic first-pass metabolism. Besides large interindividual differences in first-pass metabolism, pronounced day-to-day intraindividual variations in first-pass metabolism are observed, leading to erroneous results in relative bioavailability studies. Stable isotope techniques, which permit simultaneous administration of a solution and a tablet, can successfully be used to overcome these difficulties. The method has the advantage that two experiments can be carried out in a single test. Furthermore, the number of subjects required in bioavailability studies can be greatly reduced. Using this technique the bioavailability of verapamil tablets (Isoptin 80) relative to a stable labelled solution of verapamil was found to be 108.1%, with a 95% confidence interval between 89.1 and 127.1%.
Adult↗
Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil.
Following i.v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 1/min) approached liver blood flow (1.51/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.
Administration, Oral↗
Pharmacokinetics, bioavailability and ECG response of verapamil in patients with liver cirrhosis.
1 The pharmacokinetics, bioavailability and ECG response of verapamil was investigated in seven patients with liver cirrhosis and compared with six normal subjects, using stable labelled techniques whereby both the intravenous and oral dose are given simultaneously. 2 After intravenous administration, plasma concentrations were much higher in the patient group such that the total plasma clearance was reduced from a mean of 1258 ml/min in normals to 616 ml/min in the patient group (P less than 0.0025). The apparent volume of distribution nearly doubled (6.76 v 12.05 l/kg, P less than 0.025) and the terminal half-life was prolonged four fold (3.7 v 14.2 h, P less than 0.001). 3 Given orally, the peak plasma concentration was higher and occurred earlier in the liver cirrhotic patients. The absolute bioavailability more than doubled (22.0% normals v 52.3% liver cirrhotics, P less than 0.001) and apparent oral clearance was reduced to only 20% of normal (6.38 v 1.30 l/min, P less than 0.001). 4 The delta P-R interval in the patient group lagged behind the plasma concentration, in contrast to normal subjects. The maximum effect was much greater in the patients (15.4 v 41.6% increase, P less than 0.005) and persisted for a longer period of time. The slope of the plasma concentration-response curve was the same as in normals after intravenous administration. Plasma protein binding remained unchanged. 5 It is recommended that in liver cirrhotic patients the intravenous dose of verapamil be halved and the oral dose decreased by a factor of five in order to prevent untoward effects. As well as a steady-state plasma concentration will not be reached until approximately 2 days after the beginning of therapy.
Adult↗
Inhibition of benzo(a)pyrene-induced transformation of C3H/10T1/2 cells by allylisopropylacetamide and isopropylvaleramide.
Allylisopropylacetamide (AIA) and isopropylvaleramide (IVA) have been demonstrated previously to protect in vivo against the acute toxicity and adrenal necrotic effect of 7,12-dimethylbenz(a)anthracene. In the present study, the influence of these two amides on the in vitro transforming ability of two potent carcinogens, benzo(a)pyrene [B(a)P] and 7,12-dimethylbenz(a)anthracene, on C3H10T1/2 cells was investigated. Both AIA and IVA showed a dose-dependent inhibition of B(a)P-induced transformation of C3H10T1/2 cells when added simultaneously for 24 hr with the carcinogen. While pretreatment, simultaneous treatment, and posttreatment of the cells with AIA or IVA inhibited transformation, the 24-hr posttreatment was somewhat more effective. The protective effect did not appear to results from alterations in B(a)P metabolism inasmuch as aryl hydrocarbon hydroxylase activity and the metabolic products of B(a)P detected by high-pressure liquid chromatography were not changed by AIA or IVA treatment. Furthermore, AIA and IVA did not selectively kill chemically transformed C3H10T1/2 cells, as indicated by the absence of their effect on an established, chemically transformed cell line. AIA and IVA also inhibited 7,12-dimethylbenz(a)anthracene-induced transformation of C3H10T1/2 cells. These data suggest that AIA and IVA may be useful protective agents and that they presumably exert their protective effect at some stage between the activation of the carcinogen and the expression of the transformed phenotype.
9,10-Dimethyl-1,2-benzanthracene↗