M. Kristensen

Sulthiame (Ospolot®) as Inhibitor of Diphenylhydantoin Metabolism

The administration of sulthiame in doses of 200–800 mg daily to patients receiving diphenylhydantoin caused a rise in serum diphenylhydantoin after 1 week of combined treatment. In the doses mentioned above sulthiame increases the half‐life in the blood of injected radioactive diphenylhydantoin. Sulthiame apparently inhibits the metabolism of diphenylhydantoin in the liver, but it has not yet been possible to elucidate the mode of this inhibition.

DRUG ELIMINATION AND RENAL FUNCTION

The relationship between drug half-life and serum creatinine has recently been discussed in your journal.’ From time literature concerning drugs eliminated mainly by renal excretion, Perrier and Gibaldi have calculated endogenous creatinine production rates of 0.82 mug and 1.06 mg per minute for females and males respectively. None of these studies mention weightor age-dependent changes in creatinine production. We have studied the excretion of creatinine in time urine of 479 patients in different age groups.2’3 In men as well as in women, mean values of urinary creatinine per kilogram body weight per 24 hours were found to decrease with age, in men from 23.8±2.3 (mean±S.D.) fig in the group aged 20 to 30 years to 9.4±3.2 mg in time age group 80 to 90 years, and in women from 19.7±3.9 mg to 8.4±1.4 mg in the same age groups. These figures correspond with 1.07 mg/min/ 1.73 ni2 to 0.43 mng/min/1.73 m2 in men and with 0.83 mg/min/1.73 mtm to 0.35 mg/min/ 1.73 m2 in women. These results indicate that equations betweemi drug half-life and steady-state serum creatinine values as presented in the abovementioned study may be invalid unless it is taken into consideration how much the proportionality constant, which involves the

Electroencephalographic findings in hyperthyroidism.

Abstract 1. 1. Twenty-six of thirty-two patients with untreated thyrotoxicosis had an abnormal EEG. The severity of the hyperthyroidism evaluated by several thyroid function tests was correlated with the degree of diffuse paroxysmal activity and fast activity above 15 μV, but no correlation was found with the alpha frequency. 2. 2. After 2–6 weeks of treatment the EEGs showed a decrease in the alpha frequency parallel to the normalization of the thyroid function tests. The paroxysmal and fast activities subsided gradually and incompletely but significantly, while the slow activity did not show any significant decrease after 2–3 years. At the end of the observation period more than half of the patients still had EEGs which were abnormal, although less pronounced. 3. 3. Six patients with relapses of hyperthyroidism had aggravation of the EEG abnormalities, which again subsided after treatment was reinstituted. 4. 4. It is concluded that hyperthyroidism causes a characteristic pattern of severe EEG changes which may only subside gradually and incompletely, indicating persisting cerebral dysfunction in spite of an otherwise successful treatment of the hyperthyroidism.