Biomedical subjects

J Drewe

Publications and source records attributed to J Drewe.

113 records · Page 7Linked to original sources

PubMed1988

Differential effect of food on kinetics of bromocriptine in a modified release capsule and a conventional formulation.

The influence of food on release of drug from a modified release capsule of bromocriptine 5 mg (Parlodel SRO) and a conventional formulation of bromocriptine 5 mg has been studied in 8 healthy male volunteers. Both formulations produced objective and subjective effects, such as orthostatic reactions, nausea, dizziness, vomiting and nasal congestion. The modified release capsule caused fewer side-effects than the normal capsule. Both formulations had less cardiovascular effect in the fed than in the fasting state. There was no significant difference between the normal and the modified release capsules taken fasting or after a meal in terms of the AUC extrapolated to infinity. The relative bioavailability of the 5 mg modified release capsule was 84.6% of the normal capsule under fasting conditions and 107.5% after food. In contrast to the virtually unchanged extent of absorption, the rate of absorption was markedly affected by food, especially from the conventional capsule. The mean time of 50% absorption increased from 1.06 h (fasting) to 3.2 h (fed), whereas for the modified release capsule food mainly resulted in an increased lag time of absorption. The almost instantaneous dissolution of bromocriptine from the normal capsule in vitro (both in HCl and fasting human gastric juice) and the delay of absorption after a meal in vivo suggest that the rate limiting step in absorption of the normal capsules is delivery of released drug from the stomach to the small intestine, which is delayed by food. Both the modified release 5-mg capsule and the normal 5-mg capsule showed extended suppression of prolactin over 36 h, in all subjects, both fasted and after a meal.

Adult↗

PubMed1988

Effect of vitamin D status on the activity of carbonic anhydrase in chicken epiphysis and kidney.

Chickens were raised for 6 weeks from the date of hatch under red light on a vitamin D-free diet; controls were given an oral vitamin D supplement. Vitamin D-deficient animals showed decreased total serum calcium concentration and decreased DNA content in epiphysis and kidney homogenates. In calcifying epiphysis, total carbonic anhydrase (CA) activity was decreased, but activity per microgram DNA was slightly increased and specific activity was double that of the controls. Polyacrylamide gel isoelectric focusing after preparation of the enzyme showed a picture similar to that seen after parathyroid hormone (PTH) administration in chicks; therefore, this could be considered a secondary hyperparathyroidism. The CA activation was not seen in the kidney which can be explained by induction of an endogenous inhibitor protein of the cyclic AMP-dependent protein kinase exclusively in the kidney in vitamin D deficiency. In an additional experiment, chickens were raised for 3 weeks from the date of hatch under red light on a vitamin D-free diet. Daily oral substitution by different vitamin D metabolites (1,25(OH)2D3, 25OHD3, 24,25(OH)2D3) over 7 days led to CA activation compared with controls probably by restoring protein kinase activity in the kidney. Our results show that CA activity is inversely correlated with serum calcium concentrations which is in agreement with a regulatory mechanism recently proposed by us.

24,25-Dihydroxyvitamin D 3↗

PubMed1987

Absorption of an aqueous solution of a new synthetic somatostatin analogue administered to man by gavage.

To determine the local gastrointestinal absorption of a new synthetic somatostatin analogue (SMS 201-995 = Sandostatin), an intestinal tube was passed in eight healthy volunteers and on different days an aqueous solution was administered at four different locations: stomach, proximal duodenum, ligament of Treitz and jejunum. In a follow-up study, an oro-ileal tube was passed in six of the original volunteers and the drug solution was administered in to the terminal ileum. The aqueous solution of SMS was rapidly absorbed from the gastrointestinal tract after local application, and it was well tolerated. Absorption of the drug from the different sites was comparable, although there was a tendency to decreased peptide absorption after ileal administration. Absorption of the drug was quite variable between the subjects and the different locations. The dose-corrected systemic availability relative to subcutaneous administration in another study was 0.28%. However, significant plasma SMS concentrations were achieved, suggesting that oral delivery of the polypeptide may eventually be possible for long-term treatment of a variety of disorders.

Adult↗

PubMedDate not supplied

Current concepts in intestinal peptide absorption.

Today there is considerable interest in oral peptide delivery. However, oral administration of peptides is limited by a low bioavailability and a high variability in plasma levels. A review is given of the literature describing the major barriers in peptide absorption, the basic mechanisms of intestinal peptide transport, the experimental models and the pharmaceutical approaches currently used in the investigation of peptide and protein absorption processes.

Animals↗

PubMedDate not supplied

Hyperosmolarity does not contribute to transient radicular irritation after spinal anesthesia with hyperbaric 5% lidocaine.

BACKGROUND AND OBJECTIVES: In addition to major neurologic injury, local anesthesia toxicity may also include less severe but more common neurologic side effects. The authors recently observed symptoms suggestive of transient radicular irritation in one third of patients after spinal anesthesia with hyperbaric 5% lidocaine, whereas evidence of neurologic symptoms was lacking with hyperbaric 0.5% bupivacaine. The purpose of this prospective double-blinded study was to evaluate if the high osmolarity of hyperbaric 5% lidocaine solution might contribute to the development of transient radicular irritation. METHODS: Forty-four patients undergoing brief gynecologic procedures under spinal anesthesia were randomly allocated to receive 1.5 mL of one of three study drugs: 5% lidocaine in 7.5% dextrose (drug A), 0.5% bupivacaine in 8.25% dextrose (drug B), or 5% lidocaine in 2.7% dextrose (drug C). Drug C was prepared by the pharmacy (University Hospital, Basel, Switzerland) with an osmolarity similar to that of drug B. Drugs A and B were commercially available. Patients were evaluated on postoperative day 1 for symptoms of transient radicular irritation by an anesthesiologist who was unaware of the drug given or details of the anesthetic technique. RESULTS: Symptoms suggestive of transient radicular irritation were observed with a similar high incidence in patients receiving both lidocaine preparations, but in no patient receiving hyperbaric 0.5% bupivacaine (P < .01). CONCLUSIONS: The results suggest that transient radicular irritation did not result from the marked hyperosmolarity of the hyperbaric 5% lidocaine. However, because lidocaine and bupivacaine were not administered at equipotent dosages, the relative potential for both drugs to induce transient radicular irritation remains to be determined.

Adult↗