A multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy. The Paediatric EPITEG Collaborative Group.

The long-term efficacy and adverse-event profiles of sodium valproate and carbamazepine in children with newly diagnosed primary generalised or partial epilepsy were compared at 63 outpatient clinics. Children with two or more generalised tonic-clonic or partial seizures in the previous six months were randomised to oral sodium valproate (N = 130) or oral carbamazepine (N = 130) and followed for three years as outpatients. Dosages were increased as needed until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine were equally effective in achieving high levels of seizure control in both primary generalised seizures and partial seizures with or without generalisation. Adverse events were mostly mild, few necessitating drug withdrawal. Those particularly associated with valproate were weight increase, alopecia and appetite increase, and with carbamazepine, rashes, somnolence, diplopia and abnormal gait/ataxia.

A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group.

The long-term efficacy and safety of sodium valproate and carbamazepine in adult outpatients with newly diagnosed primary generalised or partial and secondarily generalised seizures were compared in a randomised, open, multicentre study at 22 neurology outpatient clinics. Patients were randomised to oral sodium valproate (Epilim EC enteric coated 200 mg tablets twice daily, n = 149) or oral carbamazepine (100 mg twice daily increasing to 200 mg twice daily in week 2, n = 151) and followed up for three years. If clinically necessary, dosages were regularly increased until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine controlled both primary generalised and partial seizures equally effectively overall. Significantly more patients on sodium valproate than carbamazepine (126/140 (90%) v 105/141 (75%), p = 0.001) remained on randomised treatment for at least six months. Skin rashes occurred significantly more often in carbamazepine recipients than in sodium valproate recipients (11.2% v 1.7%, p < 0.05) and carbamazepine was associated with a higher withdrawal rate because of adverse events (15% v 5% on sodium valproate) in the first six months of treatment. There was no difference between the drugs in the rate of withdrawal because of poor seizure control at any stage, regardless of seizure type. At the end of the three year trial period, over 70% of the available patients were still on randomised treatment or had recently stopped treatment after achieving full seizure control. Sodium valproate and carbamazepine were both associated with a high degree of overall seizure control regardless of seizure type and both have good long-term tolerability in adult patients with newly diagnosed epilepsy. Recommendations are made for a higher initial dosage regime for sodium valproate in partial seizures.

Bifluranol, a novel fluorinated bibenzyl anti-androgen, its chemistry and disposition in different animal species.

The synthesis of bifluranol, a new fluorinated bibenzyl anti-androgen, and of 3H-labelled bifluranol is described. The absorption, distribution and excretion of bifluranol has been studied in mouse, rat, ferret and dog; it is readily absorbed following oral administration, but blood concentrations of the drug are low due to hepatic uptake and biliary excretion. Enterohepatic re-circulation occurs, but the drug is excreted primarily in the faeces and only small amounts appear in urine. This pattern of disposition and excretion is similar to that reported elsewhere for the bibenzyl, hexoestrol, and for the stilbene, diethylstilboestrol.

The metabolism of bifluranol by rat, dog and ferret.

The synthesis of monohydroxy- and dihydroxy-bifluranol, and of glucuronide and sulphate conjugates of bifluranol are described. Bifluranol administered orally to rats, ferrets and dogs at a dosage of 50 to 200 microgram kg-1 is mostly excreted in the faeces as unchanged bifluranol and bifluranol monosulphate, disulphate and monoglucuronide. The bifluranol is well absorbed and is mostly excreted in the bile, as six different conjugates, including a glucuronide sulphate found in all 3 species, and a glucuronide phosphate found only in ferret and dog bile. Hydroxylation of the aromatic rings occurs in the rat, to an extent of about 8% of the dose, but was not detected in ferret or dog.