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Biomedical subjects

A Fazio

Publications and source records attributed to A Fazio.

At least 19 recordsLinked to original sources

A liquid chromatographic assay using a high-speed column for the determination of lamotrigine, a new antiepileptic drug, in human plasma.

A sensitive, specific and rapid liquid-chromatographic method for the determination of the new antiepileptic drug lamotrigine (LTG) in human plasma is described. The method involves the use of a commercially available 3-microns particle size normal-phase column and a microflow-cell-equipped ultraviolet detector. Extraction is carried out with ethyl acetate after alkalinization on a 100-microliters plasma sample containing LTG and 3,5-diamino-6-(2-methoxyphenyl)-1,2,4-triazine as internal standard. The residue is reconstituted with 50 microliters of ethanol, and 5 microliters of the final solution is injected into the column. Elution is carried out at 35 degrees C using n-hexane/absolute ethanol/35% ammonia (80/20/0.25 by volume) as mobile phase at a flow rate of 2.0 ml/min. Detection is at 313 nm. The chromatographic separation requires < 3 min and the sensitivity limit is < 0.1 mg/L. Recovery is 88-96.2%, whereas within-day and day-to-day coefficients of variation are between 4.1 and 7.7%.

Anticonvulsants

Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects.

The effect of the valpromide isomer valnoctamide (VCD, 200 mg three times daily for 8 days), an over-the-counter tranquillizer, on the elimination kinetics of a single oral dose of carbamazepine-10, 11-epoxide (CBZ-E, 100 mg) was investigated in healthy subjects. During VCD treatment, the half-life of CBZ-E was prolonged significantly compared with control (19.7 +/- 6.7 h vs 6.9 +/- 2.0 h, means +/- s.d., P less than 0.01), and its oral clearance decreased four-fold (from 109.6 +/- 30.7 to 28.8 +/- 11.1 ml h-1 kg-1, P less than 0.01). These findings indicate that VCM, like valpromide, strongly inhibits epoxide hydrolase in vivo.

Administration, Oral

Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction.

The effect of viloxazine (150-300 mg daily for 21 days) on plasma phenytoin levels at steady state was examined in 10 epileptic patients stabilised on a fixed phenytoin dosage. After starting viloxazine treatment, plasma phenytoin concentrations increased by 37% on average (range 7-94%) from a mean value of 18.8 micrograms/ml at baseline to a mean value of 25.7 micrograms/ml during the last week of combined therapy. In four patients the rise in plasma phenytoin was associated with the development of signs of phenytoin toxicity. Discontinuation of viloxazine resulted in return of plasma phenytoin towards baseline values and disappearance of the clinical symptoms. The mechanism of interaction probably involves inhibition of phenytoin metabolism by viloxazine. Careful monitoring of plasma phenytoin levels is recommended in patients treated with phenytoin who need to be started on viloxazine therapy.

Adult

Possible severe thrombocytopenia associated with a single dose of plicamycin.

OBJECTIVE: To report a case of possible severe thrombocytopenia associated with administration of a single dose of plicamycin. CASE SUMMARY: A 73-year-old man with prostate cancer was admitted to the hospital with hypercalcemia (total serum calcium concentration 4.02 mmol/L) and a low baseline platelet count (152 x 10(9)/L). Because of his symptomatic hypercalcemia, he was treated with NaCl 0.9%, furosemide, oral inorganic phosphate, and a single dose of plicamycin (15 micrograms/kg). Five days after plicamycin administration his platelet count decreased to 52 x 10(9)/L, and continued to decrease further even after the transfusion of four units of platelets to a nadir of 7 x 10(9)/L (hospital day 20). A second transfusion produced a small increase in his platelet count. The patient's clinical status continued to deteriorate, however, and he subsequently died. DISCUSSION: Plicamycin and other drugs that may induce thrombocytopenia are reviewed. The time course between plicamycin administration and the development of thrombocytopenia in our patient is assessed. Other contributing factors such as a low baseline platelet count and advanced age are also addressed. CONCLUSIONS: It is likely that the severe thrombocytopenia experienced by our patient was caused by a single dose of plicamycin. Adjusting the dosage for a patient's renal function as well as close monitoring of the platelet count are necessary when administering this drug. We report this case to remind clinicians of the potential for the development of severe thrombocytopenia following administration of a single dose of plicamycin.

Aged

Oral contraceptive drug interactions: important considerations.

Interactions with oral contraceptives (OCs) occur with drugs commonly used to treat epilepsy, tuberculosis, and depression. Most women are more likely to use antibiotics, analgesics, and antihistamines, which have also been shown to interact with OCs. The mechanisms behind these interactions may be hepatic microsomal enzyme induction or inhibition, interference with the enterohepatic circulation of steroid metabolites, interference with absorption, competition between two drugs for the same metabolizing enzyme, or induction of an opposite physiologic effect. Rifampin was the first drug reported to interfere with the efficacy of OCs. The anticonvulsants and certain antibiotics, namely ampicillin and tetracycline, also decrease the efficacy of OCs. Oral contraceptives also interfere with the metabolism of other drugs. Plasma concentrations of theophylline, diazepam, and certain other benzodiazepines are increased by OC steroids. Because OCs interact with a wide variety of prescription and over-the-counter medications, a thorough drug history should be taken in all patients taking OCs.

Anti-Bacterial Agents

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

Successful treatment of neonatal Citrobacter freundii meningitis with ceftriaxone.

Citrobacter meningitis is an uncommon enteric gram-negative infection that afflicts neonates and young children. Approximately 30 percent of children treated or untreated die from the infection. We report a case of C. freundii meningitis that was resistant to ampicillin and was successfully treated with ceftriaxone, a third-generation cephalosporin. A 13-day-old, full-term baby was admitted to the hospital with a one-day history of fever up to 38.8 degrees C. On admission the infant had a temperature of 39.2 degrees C, pulse of 140 beats/min, and a respiratory rate of 32 breaths/min. Except for a slightly bulging fontanelle, the rest of the physical examination was within normal limits. Complete blood count revealed a white blood cell (WBC) count of 12.5 x 10(9)/L, with 0.66 polymorphonuclear cells, 0.10 bands, 0.18 lymphocytes, and 0.06 monocytes. A stat lumbar puncture showed 10 WBCs per high-power field with gram-negative rods. Empiric therapy with ampicillin 225 mg q12h and gentamicin 11 mg q8h was started. Both antibiotics were discontinued after culture and sensitivity results were positive for C. freundii in the blood and spinal fluid. The patient was successfully treated with nine days of ceftriaxone 250 mg q12h.

Ceftriaxone

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

[The role of endorectal echography for determining the extent of an operation].

The paper discusses the usefulness of endorectal echotomography and adenolymphoscintigraphy--two new diagnostic methods which allow surgeons to know preoperatively tumor extension beyond the rectal wall and lymph nodes involvement. Though the statistical data presented are not numerous, it is hoped that, using these two diagnostic methods in cases of rectal tumors, surgeons will be able to choose better between local excision and abdominoperineal resection thus avoiding unnecessary and mutilating operations.

Adult