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Biomedical subjects

M Garle

Publications and source records attributed to M Garle.

At least 37 records · Page 2Linked to original sources
PubMed1982

Extradural pethidine with and without adrenaline during labour: wide variation in effect.

The pain-relieving effect of a single extradural dose of pethidine 25 mg with and without adrenaline was studied in 20 healthy women during labour. The study was open regarding the effects of pethidine but double-blind regarding the addition of adrenaline. In 14 of 19 women good or excellent analgesia was achieved for a period of 50-160 min. Pethidine with adrenaline 25 micrograms was not more effective than pethidine alone. Eight of the 14 women showed signs of regional analgesia to pin-prick and temperature discrimination. The patients had small (45-188 ng ml-1) concentrations of pethidine in plasma. In eight patients the plasma concentrations of pethidine were maintained for at least 1.5 h. Extradural pethidine thus induces analgesia of short and variable duration. Repeated doses may be needed, resulting in accumulation of the drug in plasma with the risk of respiratory depression in mother or child.

Anesthesia, Epidural↗
PubMed1982

Regional epidural analgesia: kinetics of pethidine.

Low intrathecal doses of opiates produce dose-dependent long-wasting elevation of the pain threshold in rats. The effect is postulated to be mediated by a direct action on the substantia gelatinosa of the spinal cord. Eight uncontrolled and two controlled studies in man showed a long duration of analgesia for most patients in the postoperative period. The duration of effect differs widely within and between studies. Using a double-blind design, we compared the relative efficacy of epidural and parenteral pethidine to control postoperative pain after total hip replacement. Preliminary pharmacokinetic data from six patients show that epidural doses of 20 or 60 mg pethidine give a similar pattern of absorption and elimination in plasma as 2 mg pethidine/kg body weight intramuscularly. The terminal elimination half-lives of pethidine in plasma are 5-7 h for all routes of administration. The possibility cannot be excluded that the analgesic effect of epidural pethidine is partly systemically mediated.

Anesthesia, Conduction↗
PubMed1982

Separate and combined use of terbutaline and theophylline in asthmatics. Effects related to plasma levels.

The bronchodilating properties and side effects of theophylline and a beta 2-adrenoceptor stimulating drug (terbutaline) alone and in combination were studied in 10 adult asthmatic patients. Initially, each individual's pharmacokinetic parameters for theophylline were determined. On 3 separate days theophylline was infused to defined steady-state concentrations (0, 7.5, and 15 microgram/ml, respectively) followed by the administration, at 1-h intervals, of incremental i.v. doses of terbutaline. It was shown that: 1. Theophylline caused a concentration-dependent increase in FEV1. Theophylline itself had no significant effect on objectively recorded skeletal muscle tremor or heart rate but enhanced the terbutaline-induced increase in tremor and heart rate. At the highest concentration (15 microgram/ml) two of the patients experienced nausea. 2. Terbutaline caused a concentration-dependent increase in FEV1, heart rate, and tremor. The plasma levels of terbutaline at the given doses did not differ significantly between individuals or within individuals at the different theophylline levels. 3. The combination of theophylline and terbutaline resulted in a mere additive effect on the bronchodilatation. At comparable bronchodilatation the combination of theophylline and terbutaline caused a lesser degree of side effects than each of the drugs alone.

Adult↗
PubMed1979

Techniques for plasma protein binding of demethylchlorimipramine.

The cerebrospinal fluid (CSF) and plasma levels of demethylchlorimipramine (DMCI) were determined during treatment of depression or obsessive-compulsive disorders with chlorimipramine. In 18 patients the mean CSF/plasma ratio of DMCI was 2.6% +/- 0.7 SD with fourfold variation (1.1% to 4.0%). In spite of this variation, the levels in CSF and plasma at steady state correlated closely (r = 0.91; p less than 0.001). With equilibrium dialysis for the determination of the protein binding of DMCI, a much higher free fraction was found in patients (8.0 +/- 1.6%) and in control subjects (8.2 +/- 1.4%). It was shown that part of the plasma binding capacity was lost during the incubation. Results obtained by ultrafiltration (3.9 +/- 1.0% unbound drug) were closer to the in vivo results, but this method also had disadvantages; much of the drug was absorbed on the ultrafiltration dialysis membrane. Our results suggest that there is a need for care in the selection of a technique for studies of drug protein binding.

Blood Proteins↗
PubMed1979

Plasma levels and renal excretion of phenytoin and its metabolites in patients with renal failure.

Phenytoin (DPH) and its two major metabolites, conjugated and unconjugated 5-(4-hydroxyphenyl)-5-phenylhydantoin (4-OH-DPH), have been studied in plasma and urine to 4 healthy subjects and 3 uremic patients during two weeks on DPH, 0.1 gm daily. Only 0.4% to 1.2% of the dose was excreted as unchanged DPH. The DPH concentrations in urine were in the same range as calculated unbound levels of DPH in plasma in the normal subjects; 1% to 2% of the dose was excreted as unconjugated 4-OH-DPH in the normal subjects. In the uremic patients, renal clearance of this metabolite was reduced to one-sixth that percentage. Plasma concentrations rose to values twice as high as normal, indicating increased rate of glucuronidation. Urinary recovery of conjugated 4-OH-DPH in healthy subjects was 52% to 94%. Its renal clearance was close to glomerular filtration rate when corrected for protein binding, suggesting elimination by glomerular filtration rate when corrected for protein binding, suggesting elimination by glomerular filtration only. Plasma concentrations of conjugated 4-OH-DPH reached plateau levels around day 4 in normal subjects. In the uremic patients, plasma concentrations of this metabolite accumulated to levels 10 times normal, and after 15 days of medication plateau levels did not seem to have been reached.

Adult↗
PubMed1977

Effect of simultaneous treatment with low doses of perphenazine on plasma and urine concentrations of nortriptyline and 10-hydroxynortriptyline.

Plasma levels of nortriptyline and perphenazine were measured in six patients on continuous nortriptyline treatment before, during and after oral administration of perphenazine 4 mg t.i.d. In four patients the plasma levels of the conjugated and unconjugated principal metabolite 10-hydroxynortriptyline were also measured. Urinary excretion of conjugated and unconjugated 10-hydroxynortriptyline and plasma levels of perphenazine were determined in all six patients. During treatment with perphenazine two patients showed a slight increase in the plasma level of nortriptyline. The changes in metabolite excretion rate were inconclusive. Thus, there did not appear to be any important pharmacokinetic interaction between the two drugs at the doses used, which were normal therapeutic doses. The previously reported inhibitory effect of perphenazine on the metabolism of nortriptyline probably depended therefore, either on administration of a higher dose of perphenazine, or on treatment in the reverse sequence--a single dose of nortriptyline was given to patients already receiving perphenazine.

Adult↗
PubMed1977

Plasma concentrations of 5-(4-hydroxyphenyl)-5-phenylhydantoin in phenytoin-treated patients.

A mass fragmentographic method was used to determine unconjugated and conjugated 5-(4-hydroxyphenyl)-5-phenylhydantonin (4-OH-DPH) in plasma of patients being treated with phenytoin (DPH). The plasma concentration of unconjugated 4-OH-DPH is stable at steady-state for DPH and the level does not change during the dose interval. Most patients (82.5%) have plasma concentrations of unconjugated 4-OH-DPH between 0.04 and 0.2 mug/ml at concentrations of DPH between 5 and 30 mug/ml. Interindividual differences in the ratio between plasma concentration of unconjugated 4-OH-DPH and DPH were noted in a wide range of doses. Dosage adjustments of DPH in patients were not associated with major changes in the plasma level of unconjugated 4-OH-DPH. The plasma concentration of conjugated 4-OH-DPH also showed interindividual differences and varied between 1.2 and 4.5 mug/ml in patients with DPH concentrations between 5 and 30 mug/ml. The data are consistent with the concept of Michaelis-Menten kinetics for DPH metabolism.

Dose-Response Relationship, Drug↗
PubMed1977

Identification of nonpolar methotrimeprazine metabolites in plasma and urine by GLC-mass spectrometry.

Two metabolites of methotrimeprazine, the sulfoxide and the demethylated analog, were identified in extracts from patient plasma by combined GLC-mass spectrometry. Methotrimeprazine and its sulfoxide had similar mass spectra but different GLC retention times. In addition to the metabolites found in plasma, two other metabolites, the didesmethyl analog and the monodesmethyl sulfoxide, were identified in a urine extract.

Adult↗
PubMed1976

Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses.

A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorathidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n = 10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those preducted from the single oral dose studies in healthy volunteers.

Adult↗
PubMed1976

Mass fragmentographic determination of diphenylhydantoin and its main metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, in human plasma.

A method is described for the mass fragmentographic determination of diphenylhydantoin and its main metabolite, 5-(-4-hydroxyphenyl)-5-phenylhydantoin (4-OH-DPH), in human plasma as their dimethyl and trimethyl derivatives, respectively. The derivatives are formed by using the recently described extractive alkylation technique. Pentadeuterated 4-OH-DPH is used as the internal standard. Following acidic hydrolysis of the plasma sample, conjugated 4-OH-DPH and, indirectly, the dihydrodiol metabolite, 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin, are measured. Using 100-mul plasma samples, the lower limit of detection is about 10 ng/ml 00.03 nmole/ml).

Alkylation↗
PubMed1975

Assay of the major (4-hydroxylated) metabolites of diphenylhydantoin in human urine.

A modified gas chromatographic procedure for the determination of unconjugated and conjugated 4-hydroxydiphenylhydantoin (4-OH-DPH) in urine has been developed. Unconjugated 4-OH-DPH is determined after selective extraction with toluene-ether (1:1). For the assay of conjugated 4-OH-DPH, the urine is pre-extracted with isoamylalcohol before acid hydrolysis to avoid interference by the dihydrodiol metabolite of DPH. The sensitivity of the method is 0.1 mug per ml. The method has been used to determine the urinary metabolites in two adult volunteers, during steady state plasma concentrations of DPH and in the elimination phase.

Adult↗
PubMedDate not supplied

Use of khat in lactating women: a pilot study on breast-milk secretion.

Nor-pseudoephedrine, one of the active ingredients of khat (Catha edulis), was found to be excreted in breast-milk in several lactating women who were chewing the leaves of the shrub according to the local customs. The compound could be traced in the urine of one breast-fed infant. It is concluded that the use of khat during lactation should be discouraged until further research has clearly elucidated the potential health hazards.

Catha↗