Biomedical subjects

S Schwabe

Publications and source records attributed to S Schwabe.

5 recordsLinked to original sources

PubMed1995

The Neurotoxicity Scale: the validity of a patient-based scale, assessing neurotoxicity.

The validity of a patient-based scale, presumably measuring adverse effects of drugs on cognitive function, was examined in a normal volunteer study. Thirty subjects were randomly assigned to placebo or one of two doses of a benzodiazepine, temazepam (10 mg and 20 mg), in a double-blind placebo-controlled parallel group design. Plasma samples were taken before the scale was completed and up to 8 hours post-dose. After administration of the medication the subjects were asked to maintain their normal daily routine as much as possible (reading, studying, conversations). The inventory was administered twice, at 50 minutes and 2 hours post-dose (peak level). The overall score was different between the three groups, only for the second assessment, 2 h post-dose (ANOVA, P < 0.02). Multiple t-testing between the three groups revealed statistically significant differences between placebo and the 10 mg temazepam group (P = 0.02) and between placebo and the 20 mg temazepam group (P = 0.006). No significant difference was found between the two temazepam groups. Analysis of the separate questions showed least sensitivity for questions related to the domain of 'hyperexcitability' and most sensitivity for 'fatigue' and 'slowing.' The overall score appeared to be sensitive already for the lower toxicity range suggesting an 'all or nothing effect'. The subjective reports, collected by using this scale, may therefore be used for the detection of gross overall changes in cognitive functioning.

Adult↗

PubMed1994

Clinical development outlook of oxcarbazepine.

Oxcarbazepine (OCBZ) has been accepted for registration as a first-line antiepileptic drug (AED) in several countries. However, because of changing regulations, further studies confirming statistically significant proof of efficacy are necessary in accordance with new standards. Therefore, Ciba has initiated a worldwide clinical development program to achieve registration. Four different types of design to demonstrate statistically significant proof of efficacy in partial seizures will be initiated. These studies are a "classical" polytherapy add-on study, a monotherapy substitution trial, a high-dose/low-dose active-control monotherapy study, and a study in presurgical patients.

Aged↗

PubMed1994

Oxcarbazepine: clinical development program.

Oxcarbazepine (OCBZ, Trileptal) is registered in several countries and has been well received by patients and physicians. However, newer standards in many other countries require additional data before registration can be achieved. For this reason, Ciba has implemented further clinical studies. OCBZ has a chemical structure that is closely related to carbamazepine (CBZ). In humans, OCBZ is not oxidatively metabolized, therefore causing little, if any, induction of hepatic enzymes. Because of this, and because of low protein-binding properties, OCBZ causes markedly fewer interactions with concomitant medications than most marketed antiepileptic drugs. OCBZ has been shown to have significantly fewer limiting side effects (described as side effects leading to discontinuation of treatment) than CBZ, while showing comparable efficacy. Many patients who are hypersensitive to CBZ can be treated with OCBZ. The usually administered dosage of OCBZ is approximately 50% higher than that of CBZ. However, better tolerability of OCBZ makes it possible to give higher dosages. The plasma concentration half-life of the active metabolite (monohydroxy derivative; MHD) makes it possible to administer OCBZ twice daily. No changes in dosage are necessary in patients with impaired renal function unless creatinine clearance is below 30 ml/min. In patients with such severely reduced creatinine clearance, the dose of OCBZ should be halved. Specific questions e.g., such as whether OCBZ causes hepatic enzyme induction at higher doses and the effect of OCBZ on intrinsic sex hormones, will be answered in future studies. In addition, the tolerability and pharmacokinetics of OCBZ in specific target populations such as the elderly, children, and hepatically impaired patients will be addressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine.

Eight healthy male volunteers (age 25-41 years) entered an open-label, within-subject study. They were treated for 13 consecutive days with felodipine (FEL) extended-release tablets, 10 mg daily. On day 6, oxcarbazepine (OXC) 600 mg was given in the morning, and from day 7 to 13, the daily dose was increased to 450 mg b.i.d. Blood samples for measurement of FEL and its pyridine metabolite (determined by gas-chromatography) were drawn just before dosing and at 2, 4, 6, 8, 10, 12, and 24 h after dosing on days 5, 6, and 13. Steady-state pharmacokinetic parameters of FEL and its pyridine metabolite were not influenced by the single dose of OXC. Repeated coadministration of OXC significantly reduced the area under the concentration-time curve (AUC0-24) of FEL by 28% and the FEL maximum plasma concentration (Cmax) by 34%. This reduction in FEL bioavailability is much smaller than that observed after co-administration of carbamazepine (CBZ) (i.e., 94%).

Administration, Oral↗

PubMedDate not supplied

Hyponatremia associated with carbamazepine and oxcarbazepine therapy: a review.

Hyponatremia, an electrolyte disturbance usually without clinical significance, may sometimes lead to serious complications when overlooked or not treated appropriately. One cause of hyponatremia, the syndrome of inappropriate antidiuretic hormone (SIADH) secretion, has been associated with some drugs, including carbamazepine (CBZ). Because of its antidiuretic effects, CBZ has been used successfully to treat diabetes insipidus centralis. Possible mechanisms for the antidiuretic effects of CBZ have been proposed. Altered sensitivity to serum osmolality by the hypothalamic osmoreceptors appears likely, but an increased sensitivity of the renal tubules to circulating ADH cannot be excluded. CBZ has led to hyponatremia in patients with epilepsy, neuralgia, mental retardation, and psychiatric disorders with a frequency varying from 4.8 to 40%. Oxcarbazepine (OCBZ), which is structurally related to CBZ, has shown similar hyponatremic effects, but whether hyponatremia occurs more often than with CBZ is not yet clear. Experience with OCBZ is still limited, and there is no definite explanation for a possible difference in antidiuretic potency. Most patients with CBZ/OCBZ-induced hyponatremia are asymptomatic. In rare cases, water intoxication has been reported, necessitating treatment discontinuation.

Carbamazepine↗