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Biomedical subjects

E S Neiss

Publications and source records attributed to E S Neiss.

32 records · Page 2Linked to original sources
PubMed1978

Cephradine and epicillin in body fluids of lactating and pregnant women.

The passage of two antibiotics, cephradine and epicillin, into the milk of 12 lactating women and the amniotic fluid of 48 pregnant women was investigated. All women were given a 500-mg capsule every six hours for at least two days prior to our taking multiple biologic samples from them. Constant levels of both antibiotics were reached in the milk of lactating women as well as in the amniotic fluid of mid-term and full-term pregnant women during the sample period. The ratio of drug concentrations in serum to that in milk was about 5.0 for each antibiotic. In the midtrimester women, the ratio of concentrations in serum to amniotic fluid of both antibiotics was approximately 1.0, suggesting the development of an equilibrium between these two compartments. This ratio was 0.2 for both drugs in the full-term women, demonstrating that the antibiotics concentrated in the amniotic fluid compartment.

Amniotic Fluid↗
PubMed1976

Absorption and excretion of a new antidepressive (SQ 10,996) in humans.

A single oral dose of 10 mg of SQ 10,996-14C was absorbed slowly by 3 normal male volunteers, with peak plasma concentrations achieved 6 hr after ingestion; the plasma half-life was about 38.5 hr. On average, 82.3 +/- 3.5% of the radioactivity present in the 2 hr plasma sample was bound to plasma proteins. These volunteers excreted an average of 31 and 52% of the dose in the urine and feces, respectively. All subjects excreted minor amounts of 14CO2 in the expired air. No unchanged SQ 10,996-14C was found in the urine. Three unidentified metabolites were excreted in urine. SQ 10,996-14C was excreted in the feces only as unchanged drug, suggesting that the drug is incompletely absorbed. The volunteers tolerated the drug well and experienced no adverse effects.

Administration, Oral↗
PubMed1975

Sex differences in the intramuscular absorption and bioavailability of cephradine.

Six male and six female volunteers each received a single intramuscular injection of cephradine, a new cephalosporin antibiotic, once weekly for 3 consecutive weeks. The drug was injected into the gluteus maximus, vastus lateralis, or deltoid muscle groups. Injection sites were rotated each week so that each subject received an injection into each muscle. Pharmacokinetic evaluation of serum concentrations and urinary excretion data indicated a sex difference with respect to the rate and extent of cephradine absorption from the three injection sites. Smaller areas under the curve and absorption rate constants were observed for females after injection into each muscle group. The most striking difference was observed when cephradine was injected into the gluteus maximus muscle, where the exponential function describing the alpha phase was observed to be 1.16 +/- 0.17 hr(-1) for females and 2.70 +/- 0.34 hr(-1) for males. Total area under the mean serum concentration-time curves, mean time to peak, and peak height parameters consistent with the slower rate of absorption and lesser bioavailability in females were observed. These results show that the vastus lateralis or deltoid muscle groups are preferable to the gluteus maximus as injection sites because of the more rapid rates of drug absorption from those muscles.

Absorption↗
PubMed1975

Absorption and biotransformation of topically applied 8-(methylthio) cyclic AMP. Studies in dogs and humans.

8-(Methylthiocyclic AMP-35S was applied topically to the intact or abraded skin of dogs at a dose of about 2-5 mg/kg. In this species, an average of 7% of the dose was absorbed through the intact and 62% through abraded skin. Half-lives for radioactivity in plasma averaged 3-6 h. After the topical application of the drug to the intact skin of dogs, the average concentration in plasma of glucose, but not of insulin, was increased by as much as 21%; after application to abraded skin, glucose and insulin were increased, on average, by as much as 84 and 221%, respectively. 8-(methylthio)adenosine and two unidentified compounds were present as metabolites in the urine of dogs; some unchanged 8-(methylthio)cyclic AMP-35S was also excreted. 8-(methylthio)cyclic AMP-35S was also applied topically (25 mg; 0-32 mg/kg) to the intact and stripped skin of normal human subjects under conditions similar to those used for dogs. Three subjects with intact skin did not absorb any of the drug, whereas three subjects with stripped skin absorbed 0-5, 8-3, and 23-3% of the dose. The half-life of radioactivity in the plasma of the subject with the greatest absorption was 0-5 h during the first 2 h, and 11 h for the next 10 h. During the first 2 h, this same subject excreted unchanged drug and 8-(methylthio)adenosine in his urine. No changes in glucose or insulin concentrations in plasma were observed in any of the subjects nor was there any apparent irritation of the skin.

Adenosine↗
PubMed1975

Clinical pharmacology of SQ 10,996, a potential antidepressive agent.

Single oral doses of SQ 10,996 ranging from 500 to 1000 mg (0.34 to 15.3 mg/kg), given once daily for 3 consecutive days to groups of healthy volunteers, were well tolerated. One of three subjects given 1250 mg (17.1 mg/kg) and two of three subjects given 1500 mg (15.6 and 21.4 mg/kg) became drowsy on the second and third days; this symptom disappeared within 24 hrs after cessation of dosage. A short-term, multiple-dose tolerance study was carried out with a formulation of SQ 10,996, the bioavailability of which was comparable to that of the formulation used earlier in the ascending-dose tolerance study. When 200-mg doses were administered every 12, 8, or 6 hrs over a 6-day period, mean steady-state serum concentrations of approximately 4, 7, and 8 mug/ml were attained within 48 hrs; unexpectedly, no subject showed any sign of drowsiness. The half-life for SQ 10,996 in serum, estimated from concentrations in serum after the last dose, was approximately 13 hrs, significantly shorter than the half-life found previously after the administration of single 10-mg doses. These clinical pharmacology studies in healthy volunteers have shown SQ 10,996 to be biologically available and well tolerated. Future studies will test its antidepressive potential in patients.

Adult↗
PubMedDate not supplied

The disposition of 14C-indapamide in man.

The metabolism of 14C-indapamide labeled in the indoline ring was determined after a single oral administration of a solution (4.99 mg, 90.47 microCi) to four fasted adult male volunteers. 14C-Indapamide was rapidly absorbed, and peak blood concentrations of radioactivity occurred by 0.5 hour in three subjects and at 2 hours in one subject. The mean elimination half-lives of total radioactivity were 27.0 hours in blood and 24.5 hours in plasma. The concentration of total radioactivity in blood was 5.7 times greater than in plasma, indicating extensive binding to red blood cells. Unchanged drug, as analyzed in one subject, reached a peak concentration by 0.5 hour, and had a blood half-life of 15.8 hours. Radioactivity was primarily excreted in the urine, and more than 50 per cent of the administered radioactivity was eliminated by this route in 48 hours. By eight days, 92.8 per cent of the radioactivity was recovered, with 70.3 per cent in the urine and 22.5 per cent in the feces. 14C-Indapamide was shown to be extensively metabolized, with only 7.3 per cent of the dose excreted as unchanged drug in the urine. Systemic and renal clearances of total radioactivity were 12.8 +/- 1.3 and 8.6 +/- 0.8 ml/min, respectively, while the renal clearance of unchanged indapamide, determined for one subject, was substantially lower (1.71 ml/min).

Adult↗
PubMedDate not supplied

The bronchosparing effect of celiprolol, a new beta 1- alpha 2-receptor antagonist on pulmonary function of propranolol-sensitive asthmatics.

Twelve normotensive asthmatics who demonstrated bronchoconstriction after a single oral dose of 80 mg of propranolol received (according to a double-blind, randomized, crossover design) placebo, celiprolol 200 mg, and celiprolol 400 mg at intervals of at least three days. Pulmonary function parameters were measured by whole body plethysmography just before treatment and hourly for three hours. Thereafter, terbutaline (0.5 mg), a beta2 agonist, was administered in aerosol form at 15-minute intervals for a total of five doses. This design permitted a safety assessment of the effect of placebo and celiprolol on resting pulmonary function and the evaluation of any interaction between this beta blocker and terbutaline. Propranolol 80 mg produced a statistically significant decrease in a forced one second expiratory volume and forced vital capacity, and a pronounced rise in airways resistance as compared with either dose of celiprolol or with placebo (P less than .001). The effect of celiprolol was not statistically distinguishable from placebo. Terbutaline caused further net bronchodilation after administration of celiprolol and placebo but, even at supratherapeutic doses, failed to restore pulmonary function parameters to baseline levels after treatment with propranolol. The bronchosparing effect of celiprolol may be due to its unique pharmacologic profile, which includes cardioselectivity, modest beta 2-agonist activity, and alpha 2-receptor blockade.

Adrenergic alpha-Antagonists↗