J. Mølholm Hansen

Carbamazepine-induced acceleration of diphenylhydantoin and warfarin metabolism in man.

Diphenylhydantoin half‐life was determined in 5 patients before and during treatment with carbamazepine. It caused a significant decrease in the diphenylhydantoin half‐life from 10.6 hours to 6.4 hours. Seven patients who for a period had been given diphenylhydantoin were also started on carbamazepine. This resulted in a fall in serum diphenylhydantoin levels in 3 of the patients. Alterations in warfarin half‐life, serum warfarin, and plasma prothrombin‐proconvertin concentration during carbamazepine treatment were compatible with a stimulation of warfarin metabolism. The effect of carbamazepine on diphenylhydantoin and warfarin metabolism is probably explained by an induction of the drug‐metabolizing enzyme system in the liver.

Effect of some drugs on penicillin half‐life in blood

The half‐life (T /2) of penicillin in blood was determined in 61 patients. An inverse relationship of penicillin T/2 and endogenous creatinine clearance was found. In a group of elderly patients with normal serum creatinine, penicillin T/2 was prolonged due to age‐dependent decrease in renal function. The effect of several drugs on the active renal tubular transport mechanism of penicillin was studied. Probenecid increased penicillin T/2 from an average of 40.4 to 104.3 minutes. Penicillin T/2 in the younger patients using probenecid was of the same order as penicillin T/2 in elderly individuals not using probenecid. Phenylbutazone increased penicillin T/2 almost as much as did probenecid. Sulfinpyrazone, acetylsalicylic acid, indomethacin, and sulfaphenazole in therapeutic doses increased penicillin T /2 to a smaller degree. There was no significant change in penicillin T /2 after therapeutic doses of chlorothiazide, sulfamethizole, and sulfamethoxypyridazine.

Effect of probenecid on the excretion of ampicillin in human bile

1 Ampicillin concentrations were determined in serum and bile after intravenous injection into patients with T‐tube bile drainage of 1 gram ampicillin before and during probenecid medication. The concentrations were followed up to fifteen hours after injection. 2 Probenecid increased the half‐life of ampicillin in serum from 74 minutes to 137 minutes. 3 Ampicillin concentrations in bile were higher following probenecid medication and a concentration over 5 μg/ml was obtained for 3 h longer than before probenecid. 4 The ampicillin concentrations in bile were approximately the same as those in serum both before and during probenecid medication suggesting passive transport of ampicillin from blood to bile. 5 A combined treatment of ampicillin and probenecid might be of clinical value in the therapy of cholangitis and typhoid carriers.

ESTIMATION OF FREE THYROXINE INDEX IN THE NEWBORN USING MICRO-METHODS

Abstract. Rogowski, P., Siersbæk‐Nielsen, K. and Mølholm Hansen, J. (Medical Department E, the Obstetrical Department, and the Department of Clinical Chemistry, Frederiksberg Hospital, Copenhagen, Denmark). Estimation of free thyroxine index in the newborn using micro‐methods. Acta Paediat Scand, 63: 201, 1974.–Thyroid function in the newborn has been studied with the purpose of establishing normal values for total plasma thyroxine, T‐3 test and free thyroxine index in the neonatal period using new micro‐methods. Total thyroxine determinations were carried out using the Sephadex column method (Tetralute®) which requires 25 to 50 µ1 plasma. The unbound TBG binding sites were evaluatid using a T‐3 Sephadex retention test (Trilute®) requiring 50 μl plasma. Free thyroxine index were calculated as the product of the two tests. 202 fullterm newborns were examined in the period 19 to 71 hours after birth and the normal range (95 % limits) for plasma thyroxine were found to be 9.2–26.0 μg/100 ml. Normal values for the T‐3 test varied between 42.5 and 64.9 % and free thyroxine index values between 510–1378 arbitrary units. The mean values of total thyroxine, T‐3 test and free thyroxine index were found to be significantly increased compared with cord blood and adult mean values indicating a physiological thyroid hyperfunction in the neonatal period. The new thyroid function tests used in the present study were found to be technical simple and are suggested to be used whenever thyroid diseases in the newborn are suspected.