The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, cefpodoxime proxetil.

The effects of alteration of gastric pH and food on the pharmacokinetics of 200 mg doses of cefpodoxime proxetil tablets were studied in two separate randomized, open label, crossover studies in healthy subjects. In the pH study (n = 17 subjects), there was a lead-in period done under fasting conditions, followed by randomization to a four-way crossover of pentagastrin (6 micrograms/kg, subcutaneously), ranitidine (150 mg orally, 10 and 2 hours before dosing with the antibiotic), sodium bicarbonate (12.6 gm), or aluminum hydroxide (120 cc). Gastric pH was determined by nasogastric aspirates before and 10 minutes after the intervention, just before the antibiotic was given. Peak plasma concentrations (Cmax) and area under plasma concentration-time curve (AUC) were highest in fasting and pentagastrin periods and were 35% to 50% lower for all of the other periods (p less than 0.0001). Gastric pH and Cmax and AUC were inversely related (r = 0.66 and r = 0.62; p less than 0.0001 for both). In the food study (n = 16 subjects), there were two lead-in periods, one done while subjects were fasting and one while they were normal diet, followed by randomization to a four-way crossover of either high or low protein diets, or high or low fat diets. There were six meals in each diet. Dosing with the antibiotic was done at the midpoint of the fourth meal. Cmax and AUC were 22% to 34% higher for all diets than for the fasting period (p less than 0.0001), whereas the time to Cmax was unchanged. These studies demonstrated that absorption of cefpodoxime proxetil is best at low gastric pH or in the presence of food, which suggests that the role of gastrointestinal function on the pharmacokinetic profile is complex.

Porcine immunoglobulin transfer after prepartum treatment with selenium or vitamin E.

Responses to prepartum injection of sows with Se and vitamin E (E) were evaluated by determining immunoglobulin (IgA, IgM, IgG) levels in the colostrum and serum of the sows and the serum of their offspring. Fifty-four sows (40 multiparous, 14 primiparous) receiving diets adequate in E and Se according to current NRC (1988) standards were randomly allotted to four treatment groups in which a single i.m. injection of saline (controls), 5 mg of Se, 1,000 IU of E, or both Se and E were given on d 100 of gestation. Sows were bled prior to and 7 d after injection, at farrowing and on d 14 and 28 of lactation. Colostral samples were collected at the initiation of farrowing. Pigs were bled 20 h postpartum and at 14 and 28 d of age. Major immunoglobulin changes in the serum of the sows due to treatment were not seen prior to parturition. Injections of Se and(or) E resulted in higher colostral IgM levels (8.4, 10.7, 9.8 and 9.6 mg/ml, respectively), but only the response from Se was significant (P less than .05). Concentrations of colostral IgA or IgG were not affected by treatment (P greater than .30). Compared with controls, all three treatments increased (P less than .10) IgM concentrations in serum from pigs at birth (28.3, 33.3, 36.0 and 33.5 mg/ml, respectively), whereas IgA and IgG concentrations were not affected (P greater than .30).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of addition of yeast culture supplement to diets of lactating cows on ruminal fermentation and microbial populations.

Six ruminally fistulated Holstein cows were utilized in a randomized block design to examine effects of yeast culture supplement on ruminal metabolism and apparent digestibility. Cows were fed a diet of 40% corn silage and 60% concentrate (DM basis). Treatments were control (supplement without yeast cells) and yeast culture supplement. Treatment periods were 6 wk. Ruminal pH, ammonia, molar proportions of acetate and isovalerate, and acetate: propionate ratio were lower and molar proportions of propionate and valerate higher in cows receiving yeast. The concentration of anaerobic bacteria tended to be higher and cellulolytic bacteria concentrations were greater in cows fed yeast than in cows receiving control diet. Supplemental yeast did not affect molar proportions of isobutyrate or butyrate, total VFA, or viable yeast concentrations in ruminal fluid. Ruminal liquid dilution rate and total tract apparent digestibilities were not different between treatments. Rate of disappearance of cellulose in vitro was lower in cows receiving yeast. Less variation in ammonia concentrations and microbial numbers suggest that ruminal fermentation was more stable in cows receiving yeast culture supplement.

The effect of oral zindotrine (MDL-257), a bronchial smooth muscle relaxant, on histamine airways responsiveness in asymptomatic asthmatics.

We evaluated the efficacy of an oral dosage form of the investigational smooth muscle relaxant, zindotrine, a novel pyridazine derivative, in counteracting histamine-induced bronchospasm in a group of 12 non-medicated asymptomatic asthmatics. Histamine inhalation challenges were performed before (control) and 45, 150, and 300 minutes after zindotrine (200 and 300 mg), or the corresponding dose of placebo was administered orally in a randomized, double-blind crossover fashion. When compared to the control state, the 300-mg zindotrine dose markedly lowered histamine airway responsiveness as indicated by a significant (P less than .01) increase in the inhaled histamine dose necessary to provoke a 20% decrease in the forced expired volume in one second (PD20FEV1) 45 minutes after drug administration. The PD20FEV1 then decreased linearly over time but remained higher than the control PD20FEV1 value (P less than .05) during the entire observation period. The 200-mg zindotrine dose failed to affect the PD20FEV1. Our data indicate that orally administered zindotrine lowers airways responsiveness to inhaled histamine in asymptomatic asthmatics in a dose-dependent and time-dependent fashion.

Changes in LH pulse frequency and amplitude in intact mares during the transition into the breeding season.

Two groups of mares were exposed to an abrupt, artificial increase or a natural increase in daylength. In both groups, mean LH pulse frequency increased with time of year and was accompanied by a reciprocal decrease in LH pulse amplitude. A non-pulsatile pattern of LH secretion was observed in some mares sampled close to the day of ovulation. Maximum mean LH pulse frequency and the onset of the breeding season occurred earlier in those mares exposed to an abrupt artificial increase in daylength. In blood samples collected frequently, mean serum LH concentrations increased in relation to time of year. However, during 60 days before ovulation, when LH pulse frequency increased, mean daily serum LH values only increased on Day -3 before ovulation. The magnitude of the periovulatory LH rise was greater before the second than the first ovulation of the breeding season. These results support the hypothesis that, in the mare, a photoperiod-induced seasonal alteration in LH pulse frequency and/or amplitude may play a role in the onset of the breeding season.

Effects of diet concentrate level and sodium bicarbonate on site and extent of forage fiber digestion in the gastrointestinal tract of wethers.

Four adult wethers (45 kg) with permanent ruminal and abomasal cannulae were used in a repeated measures Latin-square arrangement of treatments to quantitate the effects of diet concentrate level and sodium bicarbonate (NaHCO3) on site and extent of forage fiber digestion in the gastrointestinal tract. Experimental diets consisted of Kentucky-31 tall fescue hay, soybean meal and a semi-purified concentrate mixture in ratios of 95:5:0, 76:4:20, 57:3:40 and 38:2:60; NaHCO3 represented 0 or 7.5% of the concentrate mixture. Ruminal digestion (% of intake) of neutral detergent fiber (NDF) and hemicellulose decreased linearly (P less than .05), whereas acid detergent fiber (ADF) digestion responded in a cubic (P less than .05) fashion to increasing concentrate level; NaHCO3 improved ruminal digestion of NDF (P less than .10) and ADF (P less than .05), but not hemicellulose. Post-ruminal digestion (% of rumen non-degraded) of NDF and ADF tended to increase, whereas hemicellulose digestion responded in a cubic (P less than .05) fashion to increasing concentrate level; NaHCO3 decreased (P less than .05) post-ruminal digestion of all fiber fractions. Total tract digestion of NDF and ADF showed a cubic (P less than .05) response, whereas hemicellulose digestion responded in a quadratic (P less than .05) fashion to increasing concentrate level; NaHCO3 had no effect on total tract digestion of any fiber fraction. Correlations of ruminal hemicellulose digestion with mean pH (r = .33; P = .07) and minimum pH (r = .30; P = .09) were attained in a 24-h feeding cycle.(ABSTRACT TRUNCATED AT 250 WORDS)