Effect of foodstuffs on the absorption of zinc sulfate.

Single doses of zinc sulfate were given to healthy young volunteers, either in the fasting state or with various types of meals. Dairy products (milk and cheese) and brown bread decreased zinc absorption, as indicated by a significant drop in peak serum zinc levels. Zinc absorption was decreased when zinc was given in the fasting state with the same amounts of purified phosphate or phytate as those found in foods above. Experiments in vitro have shown that zinc is precipitated by phosphate and phytate at pH values close to that of the intestinal lumen. Coffee also seems to inhibit zinc absorption.

Judgments of trained observers on adverse drug reactions.

Patients (672) admitted to a department of medicine during five consecutive months were followed by an investigator who identified 110 clinical manifestations which could have been considered adverse drug reactions. From these, 42 were excluded because they did not correspond to the definition of adverse reaction or they were inadequately documented. The remaining 68 cases were submitted to three independent observers who had to reply to a series of questions; from these replies five degrees of probability for the reaction itself were deduced. Reactions (54; 49% of the manifestations reported) were considered as certain or probable by at least two observers, but only 27 rections of these (25%) were attributed to the same drug by all three observers. There was a low level of agreement between any two observers (paired agreement ratio: 0.6 to 0.7) and little difference of agreement between any one observer and each of the others (personal agreement ratio: 0.6 to 0.7).

Absence of metabolic effects of the topical carbonic anhydrase inhibitors MK-927 and sezolamide during two-week ocular administration to normal subjects.

Potential systemic effects of the racemic carbonic anhydrase inhibitor MK-927 and its S-enantiomer, sezolamide hydrochloride, after topical ocular administration were investigated in a double-masked, randomized, placebo-controlled study in 16 healthy volunteers. A controlled diet was started 4 days before initiation of treatment and continued throughout the study. For 14 days six volunteers received bilaterally one drop of 2% MK-927 (1.2 mg) q.i.d., six received one drop of 1.8% sezolamide (1.1 mg) q.i.d., and four received the common vehicle q.i.d. Blood and urine electrolytes and acid-base profiles were measured before and on days 1, 7, and 14 of treatment, and 24-hour urine samples were collected daily. All values were compared with those on the pretreatment day. Taking the circadian variations of the parameters into account, no significant treatment effect was observed in either the daily profiles or the 14-day cumulative sodium, potassium, and citrate excretions. Because the usual variability of the measured biologic parameters has been reduced markedly by the stringent requirements of this study, it can be concluded that the induction of clinically significant metabolic changes by topically administered MK-927 or sezolamide is unlikely.

Influence of food and antacid administration on fluoride bioavailability from enteric-coated sodium fluoride tablets.

The relative bioavailability of enteric-coated sodium fluoride (NaF) tablets (10 mg F-) has been assessed following administration with a standard calcium-rich breakfast or calcium-poor lunch, and 2 h before or simultaneously with antacid administration (2.4 g aluminum-magnesium hydroxide), versus intake on an empty stomach. Twelve volunteers were studied 3 times according to an open, three-way crossover design over a 24 h period at weekly intervals. Meals were found to decrease the peak serum concentration of NaF from 122 micrograms/L during fasting (after baseline subtraction) to 71 and 88 micrograms/L with breakfast and lunch respectively, and to slow its absorption rate with Tmax increasing from 3.3 to 7.3 and 11.2 hours, without altering its bioavailability. Antacid impaired the bioavailability of NaF by 80% when administered simultaneously, with AUC decreasing from 987 to 155 micrograms.h/L, but had no significant effect when taken 2 h before NaF. In conclusion, the enteric-coated NaF tablets used in this study can be administered with food or after a 2-hour delay following antacid administration, but should not be taken simultaneously with antacid.

[Psychotropic agents in elderly persons]. / Médicaments psychotropes chez les personnes âgées.

The response to narcotics, sedatives, hypnotics, antidepressants and antipsychotic drugs is modified in elderly patients. The effects of these drugs are enhanced, and dosage reduction is required. This phenomenon is gradual and occurs before any sign of senile dementia. The choice of a drug within a therapeutic class may depend on the severity of adverse reactions, some of which are particularly disturbing in elderly patients.

[Consequeces of the elimination of a combination drug. Transition from combination antisacer: attention]. / Les conséquences de l'élimination d'un médicament combiné.

Antisacer compositum, a commonly prescribed speciality which associated phenobarbitone and phenytoin in a dose ratio of 1:4, was withdrawn after demonstration of a negative interaction of this formula. A retrospective analysis is presented of phenytoin plasma levels during bitherapy and after passage to monotherapy, in 13 adult epileptics followed as outpatients. Phenytoin plasma levels increased over twofold in 12 cases, of whom 5 continued to take the same doses, while 7 received higher doses on, and in one case two weeks after, the withdrawal of phenobarbitone. Plasma level decreased slightly in the thirteenth in spite of increased doses. Five phenytoin intoxications occurred after this change of prescription: one amongst the 5 cases with identical doses, and 4 amongst the 7 cases with increased doses. The initially high levels of phenytoin tend to decrease after several months. Physicians required to change the prescription should be aware of the risk of initial intoxication and later underdosage.