Biomedical subjects

H E Marr

Publications and source records attributed to H E Marr.

4 recordsLinked to original sources

PubMed1994

The antiemetic activity of granisetron against cytostatic-treatment-induced emesis in 10- to 13-week-old ferrets.

The antiemetic activity of granisetron was examined in ferrets aged 10-13 weeks. Emesis was induced by exposure to either whole-body X-irradiation (50 Gy over 10.4 min) or cyclophosphamide (80 mg/kg i.v.) plus doxorubicin (6 mg/kg i.v.). Following exposure to whole-body X-irradiation, the young ferrets vomited with a similar latency to vomit and severity of emesis to that shown by adult animals. Granisetron (0.5 mg/kg i.v.) significantly reduced (P < or = 0.05) the number of vomits and retches and two out of four animals were completely protected. Following injection of cyclophosphamide and doxorubicin, the young ferrets showed a reduced emetic response compared to adult animals. Following a dose of granisetron (0.5 mg/kg i.v.), only one out of four ferrets vomited compared to four out of four in the control group. Further experiments showed that cisplatin (12.5 mg/kg i.v.) was unable to induce vomiting in the young ferret (n = 2). Granisetron (0.5 mg/kg i.v.) was well tolerated by the young ferret and was able to reduce significantly or completely abolish emesis induced by cytostatic treatment. The data support the use of granisetron in pediatric patients and clinical trials are currently underway in this patient population.

Aging↗

PubMed1994

Further studies of the antiemetic activity of granisetron against whole body X-irradiation or cisplatin-induced emesis in the ferret.

In ferrets, the highly selective 5-HT3 receptor antagonist, granisetron, abolished or reduced emesis induced by cisplatin (10 mg/kg i.v.) or whole body X-irradiation (50 Gy in 10.4 min) in a dose-dependent manner when administered by a variety of routes (intravenous, per os, subcutaneous, intramuscular). Complete protection from vomiting and retching was achieved with 0.5 mg/kg i.v. or p.o. granisetron. Granisetron (0.5 mg/kg i.v.) was also effective when given 6 h before cisplatin, completely protecting 50% of ferrets for a total of 10 h. Following repeat dosing, for either 4 days i.v. or 10 days p.o. before emetic challenge, granisetron (0.5 mg/kg) still retained its antiemetic activity on the 5th or 11th day. Prior treatment with cyclophosphamide (80 mg/kg i.v.) resulted in a significantly shorter time to the onset of vomiting after exposure to X-irradiation. Granisetron, but not saline, abolished vomiting and nausea when given as intervention after this combined emetic regimen. These results show that granisetron has potential flexibility for administration via a variety of different routes and also a long duration of action when used as an antiemetic against a wide range of cytostatic agents.

Animals↗

PubMed1992

Are all 5-HT3 receptor antagonists the same?

A number of 5-HT3 receptor antagonists are currently in clinical development as antiemetics. In this paper we focus on two of these antagonists, granisetron and ondansetron, and compare their antimetic activity against cisplatin (10 mg/kg i.v.)- or whole body X-irradiation (200 rads)-induced emesis in the conscious ferret. The results presented here have been discussed in the light of the recently published literature. Our data suggest that in comparison to ondansetron, granisetron is a more potent, longer acting and pharmacologically "cleaner" compound with a more conventional dose-response profile. The possible impact of these features upon the performance of these compounds in the clinic is discussed particularly with respect to dosing regimens and clinical efficacy. Differences appear to be emerging between granisetron and ondansetron in both these respects, although a direct head-to-head clinical comparison has yet to be carried out. This would involve studies monitoring a sufficiently high number of patients receiving severely emetogenic regimes to allow real clinical differences to be detected with the appropriate statistical power.

Animals↗

PubMed1991

Emerging differences between 5-HT3 receptor antagonists.

A brief review is presented of some recently described 5-HT3 receptor antagonists. These antagonists are primarily targeted for use as anti-emetics. However, evidence is emerging that there are differences in their basic pharmacology. This evidence is reviewed in terms of the selectivity of the antagonists in binding studies and also of their efficacy in emesis and gastric emptying. The possibility that these differences may translate into meaningful clinical differences between the available 5-HT3 receptor antagonists in their use as anti-emetics is also discussed.

Animals↗