RESUMEN
RICOM-1013-J (Ricinus communis var minor) administered orally once to each of 12 women volunteers at a dose of 2.5-2.7 g per 8 months, protected against pregnancy over a period of 7-8 months of study. A study of the effect of a contraceptive dose (20 mg/kg) on metabolic parameters in rat (food and water in-take, urine and faecal output and body weight) over a period of 4 months showed a slight decrease in all the parameters in the first 1-8 weeks. This effect was reversible attaining pretreatment levels from week 16. The LD(50) in an acute toxicity test in mice was 63.1 +/- 16.0 g/kg s.c. Determination of blood urea, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)) and bicarbonate (HCO$_¿3¿ ¿-¿$)as a measure of renal function and alkaline phosphatase (ALP), transaminases (GPT and GOT) and transpeptidases (GGT) as a measure of liver function showed that liver function profiles in pretreated rats were not significantly different from control (p < 0.05) on day 21 to day 150. However, serum levels of ALP and GGT at day 120 to day 150 were moderately but significantly elevated (p > 0.05) compared with the control. There were no significant changes in renal function profiles in pretreated rats (p < 0.05) compared with the control. The results of the liver and renal function profiles in women volunteers showed that there were no significant (p < 0.05) changes in renal functions on day 206 following RICOM-1013-J administration. However, serum levels of ALP and GGT showed a slight rise in about 70% of volunteers, whereas bilirubin and transaminases levels were normal. The present results indicate a very high efficacy and margin of safety of RICOM-1013-J in women volunteers. The increase in ALP and GGT in both animal and women volunteers suggest mild intrahepatic cholestatic changes which may be attributed to an oestrogenic effect of RICOM-1013-J.
Asunto(s)
Anticonceptivos Femeninos/farmacología , Fitosteroles/farmacología , Adulto , Animales , Peso Corporal/efectos de los fármacos , Anticonceptivos Femeninos/efectos adversos , Diuresis/efectos de los fármacos , Conducta de Ingestión de Líquido/efectos de los fármacos , Heces , Conducta Alimentaria/efectos de los fármacos , Femenino , Humanos , Pruebas de Función Renal , Pruebas de Función Hepática , Masculino , Ratones , Ratones Endogámicos BALB C , Fitosteroles/efectos adversos , Embarazo , Ratas , Ratas WistarRESUMEN
The seeds of Ricinus communis Linn, RICOM-1013-J, administered as a single oral dose of 2.3-2.5 g once per 12 months protected against pregnancy in 50 women volunteers for a period of one year. The antifertility and contraceptive efficacy of the seed was demonstrated in this study. Clinical observation revealed very minimal side effects. Some of the side effects investigated included headache, nausea, vomiting, weight gain, loss of appetite, raised blood pressure and dysmenorrhoea. Furthermore, both the renal and liver functions were not affected as revealed by urea, electrolyte and creatinine values as well as total bilirubin, conjugated bilirubin, serum albumin, total protein and transaminases values when compared with control values. In addition cholesterol and phospholipids were not significantly altered. When all these results are considered together, it seems unlikely that the antifertility and contraceptive efficacy of RICOM-1013-J is due to hormonal mechanisms alone since side effects, renal and liver function, and cholesterol effects attributable to oestrogen and/or progesterone were minimal in the volunteers.