Bioavailability and Pharmacokinetics of a New Sustained-Release Potassium Chloride Tablet

The bioavailability of a new sustained-release potassium chloride (KC1) tablet, designed for once-a-day dosing, was compared to a KC1 elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of 80 mEq of potassium in three equally divided doses of elixir every 6 hr and a single 80-mEq dose using four 20-mEq sustained-release (SR) tablets. The mean time to maximum rate of potassium urinary excretion was 2.2 hr for the first elixir dose and 5.5 hr after the SR tablet (P < 0.01), thereby supporting the prolonged-release properties of this formulation. After correction for baseline urinary potassium excretion, the mean total 24-hr urinary potassium excretion was 42.18 mEq for the elixir and 40.41 mEq for the SR tablet. The results indicate that the absorption pattern from the SR tablet is equal to three doses of KC1 elixir dosed 6 hr apart.     

Clinical evaluation of a potassium nitrate dentifrice for the treatment of dentinal hypersensitivity

Abstract The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment for dentinal hypersensitivity was evaluated in a double-blind study in 36 Japanese subjects who complained of cold and/or tactile hypersensitivity. The subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate dentifrice (treated group) and the other 18 a vehicle paste (control group). Both groups were instructed to brush their teeth 2 × a day. The hypersensitivity levels of the affected teeth were assessed by 2 stimuli, one tactile and the other cold air, and by the perception of pain. The results of all 3 assessment methods indicated that the potassium nitrate dentifrice significantly decreased the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a rapid decrease of positive scores for both the cold air stimulus and the subjective symptoms appeared from week 2. Although a significant decrease of the assessment score was also observed in the control group, the reduction rate of the score was much greater in the treated group by ail 3 assessment methods at weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12 weeks’examination was noted in 67% of the subjects in the treated group, but in only 6% in the control group. These results suggest the usefulness of a 5% potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity.     

Repetitive firing properties in subpopulations of the chick Edinger Westphal nucleus.

The avian Edinger Westphal nucleus, through the ciliary ganglion, controls accommodation, iris constriction, and blood flow through the choroid. In live brainstem slices, the nucleus is easily identifiable as an olive-shaped cluster of neurons dorsal to the oculomotor nerve and nucleus. Intracellular recordings from neurons in the nucleus identified two classes of responses to sustained (300 to 500 ms) injections of depolarizing current. One set of cells fired action potentials for the duration of the pulse while a second set of cells fired action potentials only transiently, during the first 50 to 100 ms, after which they remained silent regardless of the size of the depolarization. Intracellular recordings followed by injections of the fluorescent dye lucifer yellow revealed that repetitively firing cells were located in the lateral half of the nucleus while non-repetitively or transiently firing cells were located in the medial half. These locations correspond to different Edinger Westphal subdivisions which have distinct inputs and target populations. The varying firing patterns are discussed with reference to the known functions of the subdivisions in which they occur. Replacement of calcium by magnesium in the extracellular medium had no effect on the number of action potentials fired by non-repetitively firing cells, suggesting that a calcium-activated potassium current is not responsible for suppressing repetitive firing in these cells. In contrast, in repetitively firing cells removal of extracellular calcium increased the frequency of action potential discharge and decreased the amplitude of afterhyperpolarizations following single action potentials. Addition of cadmium to the bath medium had similar effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction in sodium chloride intake: effects on urinary Na, K and aldosterone output in healthy free-living adults

Eleven healthy free-living adults (six women, five men) weighed and recorded all food and drink consumed and collected all urine for two non-consecutive 7-day periods whilst eating their usual diet (Period 1) and attempting to reduce salt intake (Period 2). Bread (including pitta bread) provided on average a quarter of total Na intake of subjects in Period 1 so that wholemeal bread made without added salt was made available in Period 2. All subjects achieved substantial reductions (mean 65%) in Na intake in Period 2 with no change in K intake so that the Na:K molar ratio fell from 1.3 to 0.5. Urinary Na output closely followed intakes and there was a large increase (mean 11.2 μg/d) in aldosterone excretion with a non-significant increase in K output. Simple linear relationships which allow prediction of Na and K intake from the more easily measured urinary output were derived.     

Phase II trial of gallium nitrate,amonafide and teniposide in metastatic non-small cell lung cancer

Summary Fifty-five patients with metastatic non-small cell lung cancer (NSCLC) were entered into this phase II randomized study for evaluating three new agents: gallium nitrate, amonafide and teniposide. The patients had to have ECOG performance status 0 or 1, no prior chemotherapy, and adequate hematological, hepatic and renal functions. Forty-seven patients were eligible and evaluable. Fourteen were randomized to receive gallium nitrate, 18 to amonafide and 15 to teniposide. Seventy-four percent of eligible patients were male. The majority of patients (89%) had an ECOG performance status 1. ECOG grade 4 toxicity occurred twice in patients on gallium nitrate, seven times on amonafide and 18 times on teniposide. The cause of death was attributed to amonafide in one patient (from sepsis) and to teniposide in two patients (due to infection and leukopenia). There was no objective response in all the patients entered. The overall survival times ranged from 2 weeks to 156 weeks with a median of 23 weeks. There were no survival differences among the three treatment arms. We conclude that gallium nitrate, amonafide and teniposide are inactive in metastatic NSCLC and do not warrant any further testing in this disease.The contents of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.     

Phosphorylation of brain (Na+,K+)-ATPase alpha catalytic subunits in normal and epileptic cerebral cortex: I. The audiogenic mice and the cat with a freeze lesion.

Partially purified (Na+,K+)-ATPase (E.C. 3.6.1.3.) was investigated in the epileptic cortex of audiogenic DBA/2 mice and in the primary and secondary foci of cats with acute or chronic freeze lesions. No differences in specific activities measured at 3 mM K+ were observed between epileptic and control cortex, except an increase of enzymic activities in the primary focus of acutely lesioned cats. The (Na+,K+)-ATPase catalytic subunits were resolved by SDS-gel electrophoresis and their phosphorylation levels were measured in presence of K+ ions and phenytoin. K+ was more effective in inducing maximal dephosphorylation of (Na+,K+)-ATPase in C57/BL, with identical affinity in the two strains. Phenytoin decreased the net phosphorylation level of (Na+,K+)-ATPase by about 50% in C57/BL mice, but only by 20% in DBA/2 mice. Both K+ and phenytoin dephosphorylating influences were decreased in primary and secondary foci of acutely lesioned cats. Those changes were limited to the alpha(-) subunit. In chronic cats, the dephosphorylating step of the (Na+,K+)-ATPase catalytic subunit recovered a normal affinity to K+, but its sensitivity to phenytoin remained decreased. Those differences in K+ and phenytoin influences on brain (Na+,K+)-ATPases between control and epileptic cortex might be responsible for the ictal transformation and seizure spread. In cats, the alteration of the alpha(-) isoform could mainly affect the glial cells.     

Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi

Miconazole and econazole, two fungicide imidazole derivatives, completely inhibited growth of Trypanosoma cruzi (Tulahuen strain) at concentrations of about 20 muM. Culturing of T. cruzi in the presence of lower doses of imidazole derivatives produced: decrease of 5,7-diene sterol content in epimastigotes (including ergosterol); disappearance of the nuclear chromatin, vacuolization and decrease in the electron density of the cytoplasm; selective surface alterations as revealed by an increased response to wheat-germ- and phytohemagglutinin. At variance with the effect of miconazole on Candida (De Nollin et al. (1977) Antimicrobial. Agents Chemother. 11, 500-513), miconazole and econazole, under the experimental conditions used, did not increase the rate of hydrogen peroxide generation by T. cruzi.