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Biomedical subjects

E Spina

Publications and source records attributed to E Spina.

At least 73 records · Page 4Linked to original sources
PubMed1992

Debrisoquine oxidation phenotype and neuroleptic-induced dystonic reactions.

To evaluate the role of defective drug oxidation as a predisposing factor for neuroleptic-induced dystonic reactions, 26 patients who developed the reaction and 53 with no history of dystonia were phenotyped by the debrisoquine hydroxylation test. The percentage of poor debrisoquine metabolizers was similar in patients with dystonic reactions (11.5%) and in the control group (9.4%). These results suggest that there is no association between the individual's drug oxidative status and the occurrence of neuroleptic-induced dystonia.

Adult↗
PubMed1991

Debrisoquine oxidation phenotype during neuroleptic monotherapy.

The debrisoquine oxidation phenotype was determined in 91 schizophrenic patients on monotherapy with different neuroleptics and in 67 untreated healthy volunteers. The prevalence of poor metabolizers of debrisoquine was significantly higher in the patients (46.2%) than in the healthy subjects (7.5%). Treatment with phenothiazine antipsychotics (chlorpromazine, levomepromazine and thioridazine) was associated with a higher debrisoquine metabolic ratio than treatment with haloperidol. On the other hand, treatment with clothiapine appeared not to interfere with debrisoquine oxidation. Oral administration of 50 mg thioridazine daily to 8 healthy subjects resulted in a marked increase in the debrisoquine metabolic ratio and 4 of them were transformed into phenotypically poor metabolizers. The results confirm the fact that phenothiazines, and to a lesser extent haloperidol, inhibit the oxidative metabolism of debrisoquine. They show also that clothiapine administration does not disturb the debrisoquine metabolic ratio.

Adult↗
PubMed1991

Effect of phenobarbital on the pharmacokinetics of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine.

The single oral dose kinetics of carbamazepine-10,11-epoxide (CBZ-E), the active metabolite of carbamazepine, were studied in six epileptic patients, stabilized on phenobarbital (PB) monotherapy, and in six drug-free health volunteers. The epoxide metabolite was administered as an enteric-coated tablet at the dose of 200 mg to the patients and at the dose of 100 mg to the volunteers. Patients had a significantly higher plasma clearance of CBZ-E than the control group (mean values +/- SD = 220.2 +/- 63.5 versus 112.5 +/- 46.0 ml/h/kg, p less than 0.007) and a significantly shorter plasma half-life (mean values +/- SD = 4.3 +/- 1.0 versus 6.7 +/- 0.8 h, p less than 0.0015). These results suggest that PB induces CBZ-E metabolism.

Adult↗
PubMed1990

No effect of thioridazine on plasma concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide.

The effect of an oral treatment with thioridazine (100 or 200 mg daily) on plasma concentrations of carbamazepine (CBZ) and its active metabolite carbamazepine-10,11-epoxide (CBZ-E) was studied in eight epileptic patients stabilized on CBZ therapy. No significant changes in steady-state plasma levels of CBZ and CBZ-E occurred, suggesting that CBZ metabolism is not apparently affected by thioridazine.

Adult↗
PubMed1990

Prevalence of primary cutis verticis gyrata in a psychiatric population: association with chromosomal fragile sites.

The prevalence of cutis verticis gyrata was studied in a psychiatric institutional population of 494 patients, the majority of whom were mentally retarded or had chronic schizophrenia. Twenty-two subjects (21 males and 1 female) were found to have primary cutis verticis gyrata, yielding a prevalence of about 4.5%. The frequency of the scalp disorder was 11.4% among mentally retarded patients and 1.7% in schizophrenic subjects. A cytogenetic study was performed on patients with primary cutis verticis gyrata. In 9 out of 21 subjects there was evidence of chromosomal fragile sites: 5 patients had fragile sites on the X-chromosome, in 2 there was fragility of chromosome 12 and in 2, fragility of chromosome 9. The fragile X-site is the genetic marker of the 'fragile X-syndrome', a sex-linked inherited disorder often associated with mental retardation and other neuropathological findings.

Adult↗
PubMed1989

In vitro inhibition of a polymorphic human liver P-450 isozyme by narcotic analgesics.

Genetically determined differences in the ability of individuals to oxidize certain drugs by hepatic P-450 processes has gained increasing attention. The so-called debrisoquin hydroxylase, which is defective in approximately 5-10% of whites, is known to be of major importance for the metabolism of several drugs. The possible relation of this isozyme to the metabolism of narcotics eliminated by oxidative biotransformation has not been studied. Several narcotics were screened for in vitro interaction with this P-450 isozyme. This was accomplished by testing for competitive inhibition by narcotics of the 2-hydroxylation of desmethylimipramine in a human liver microsomal preparation. Alfentanil, fentanyl, and dextropropoxyphene were found to competitively inhibit this pathway demonstrating an interaction with this polymorphic isozyme. No interaction was found for codeine, meperidine, methadone, morphine, or nalbuphine. These results suggest that a genetic defect may be important for elimination clearance by metabolism for dextropropoxyphene, alfentanil, and fentanyl and that in vivo investigation is warranted.

Analgesics, Opioid↗
PubMed1989

Diazepam treatment does not influence the debrisoquine or mephenytoin hydroxylation phenotyping tests.

Debrisoquine and S-mephenytoin hydroxylation phenotyping tests were performed in 9 patients before and during treatment with diazepam at a daily dose of 10 or 15 mg. There was no change in either the debrisoquine/4-hydroxydebrisoquine ratio or the ratio of S/R mephenytoin in urine. The hydroxylation of these two test drugs is apparently not inhibited by administration of therapeutic doses of diazepam.

Adult↗
PubMed1989

[Systemic cardiorespiratory effects induced by doxofylline].

The authors evaluated the clinical effectiveness and tolerability of doxofylline, a new methyl-xanthinic derivative with peculiar pharmacodynamic properties. 13 patients affected with chronic obstructive lung disease (mean age +/- 54 years) were studied. Doxofylline (200 mg) and theophylline (240 mg) were randomly administered by intravenous route in 60'. Arterial haemogasanalysis, FEV1 and ECG data were obtained after the infusion. Doxofylline proved to possess an equal therapeutic efficacy in comparison to theophylline, with a better clinical tolerability. In conclusion, doxofylline is a new and effective drug for the treatment of bronchostructive disorders.

Cardiovascular System↗
PubMed1988

Inhibition of desipramine 2-hydroxylation by quinidine and quinine.

Urinary excretion of desipramine (DMI) and 2-hydroxydesipramine (2-OH-DMI) after single oral doses of 25 mg DMI was investigated in seven rapid and three slow debrisoquin hydroxylators, before and after pretreatment with either quinidine or its diastereoisomer quinine. After treatment with 800 mg quinidine daily for 2 days, excretion of 2-OH-DMI decreased by 96% in rapid hydroxylators and 68% in slow hydroxylators. After treatment with 750 mg quinine/day for 2 days, excretion of 2-OH-DMI in rapid hydroxylators was 54% lower than during the control experiment, whereas in slow hydroxylators no significant changes in the excretion pattern were observed. Unchanged DMI constituted only a minor fraction of recovered drug and no significant changes in its recovery were observed in either phenotypic group after pretreatment with quinidine or quinine. Thus both quinidine and quinine decreased the excretion of 2-OH-DMI. At similar does the effect of quinidine was much stronger than that of quinine, virtually transforming rapid hydroxylators into slow hydroxylators. The mechanism probably involves a stereoselective inhibition of DMI 2-hydroxylation.

Adult↗
PubMed1988

Alprazolam does not inhibit the metabolism of nortriptyline in depressed patients or inhibit the metabolism of desipramine in human liver microsomes.

In 10 patients treated with nortriptyline, the steady-state plasma concentrations of the parent drug and the active 10-hydroxy metabolite were very similar before and during concomitant treatment with alprazolam (0.5 mg orally t.i.d.). In human liver microsomes the 2-hydroxylation of desipramine was not inhibited by alprazolam. The absence of an inhibition by alprazolam on the hydroxylations of nortriptyline in vivo and of desipramine in vitro indicates that alprazolam is not metabolized by the debrisoquine hydroxylase.

Adult↗
PubMed1988

Evaluation of tricyclic antidepressant plasma levels by an automated enzyme immunoassay (EMIT) in comparison to a high-performance liquid chromatographic method.

A new homogeneous enzyme immunoassay technique (EMIT) for the measurement of plasma levels of amitriptyline, nortriptyline, imipramine, and desipramine was used with an automated procedure and the results were compared to those of a high-performance liquid chromatographic (HPLC) method. Precision of the EMIT test was similar to that of the HPLC method with within-day coefficients of variation in the range of 3.9-10.9% (EMIT) and 3.9-9.6% (HPLC). The day-to-day coefficients of variation ranged from 4.4 to 11.7% for EMIT and from 6.1 to 8.4% for HPLC. Samples from 124 patients were analyzed by both methods and a good correlation was observed for all the four drugs. A paired t test indicated no significant difference for the EMIT and HPLC values. No significant interferences were observed between the tricyclics tested and other commonly associated drugs, such as benzodiazepines and neuroleptics. The new EMIT assay proved to be rapid and easy to perform and showed sufficient reliability and reproducibility to be used for either emergency or routine analysis.

Antidepressive Agents, Tricyclic↗
PubMed1988

Effect of valpromide on the pharmacokinetics of carbamazepine-10, 11-epoxide.

The single oral dose pharmacokinetics of carbamazepine-10, 11-epoxide (CBZ-E) were investigated in six normal volunteers during a control session and during concurrent treatment with valpromide (VPM) (300 mg twice daily for 8 days). VPM caused a prolongation of the CBZ-E half-life from 6.4 +/- 1.4 to 20.5 +/- 6.3 h and decreased CBZ-E clearance from 73.5 +/- 20.0 to 23.5 +/- 4.0 ml h-1 kg-1 (P less than 0.01). These results suggest that the elevation of plasma CBZ-E levels in patients receiving carbamazepine and VPM in combination is due to inhibition of epoxide hydrolase in the liver.

Adolescent↗
PubMed1988

Single-dose kinetics of an enteric-coated formulation of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine.

The kinetics of an enteric-coated formulation of carbamazepine-10,11-epoxide (CBZ-E) were studied in healthy subjects. A single oral dose of 100 mg of CBZ-E was given to eight subjects. Four of them were also given a single oral dose of 200 mg of CBZ-E. Plasma concentrations of CBZ-E and urinary excretion of the end metabolite trans-10,11-dihydroxy-10,11-dihydro-carbamazepine (trans-CBZ-diol) were determined by high performance liquid chromatography. Plasma kinetics of CBZ-E fitted an open one-compartment model with plasma elimination half-life of 7.4 +/- 1.8 h (mean +/- SD). The clearance was 105 +/- 17 ml/kg/h and the apparent volume of distribution 1.1 +/- 0.2 L/kg assuming complete bioavailability. There was no indication of dose-dependent elimination of CBZ-E. The recovery of trans-CBZ-diol in urine collected for 3 days was 67 +/- 9% of the given dose. This enteric-coated formulation may thus in the future be used for the evaluation of the clinical effects of CBZ-E in patients.

Adult↗