Influence of sex difference on the pharmacological action and metabolism of some drugs

Kato, Ryuichi; Chiesara, E.; Frontino, G.

doi:10.1016/0006-2952(62)90077-1

Cited by 120 publications

(36 citation statements)

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“…For example, the administration of the phenobarbital and various drugs markedly decreased the effects of numerous drugs through increases in the activities of drug-metabolizing enzymes of liver microsomes (1-5). On the other hand, the effects of various drugs were increased in fasted or low protein diet fed rats through decreases in the activities of drug-metabolizing enzymes (6, 7).It has been reported that species and sex differences in the effects of dugs are often related to the difference in the rate of drug metabolisms (1,(8)(9)(10)(11).It is well known that there are marked individual differences in the effects of various drugs in animal and clinical experiments. On the other hand, it has been considered that such individual differences may be due to differences in the sensitivity of the target organs.…”

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Individual Difference in the Effect of Drugs in Relation to the Tissue Concentration of Drugs

Kato

Takanaka

Onoda

1969

Japanese Journal of Pharmacology

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It has been reported that the alteration in the effect of various drugs is often related to the alteration in the rate of drug-metabolism (1-10). For example, the administration of the phenobarbital and various drugs markedly decreased the effects of numerous drugs through increases in the activities of drug-metabolizing enzymes of liver microsomes (1-5). On the other hand, the effects of various drugs were increased in fasted or low protein diet fed rats through decreases in the activities of drug-metabolizing enzymes (6, 7).It has been reported that species and sex differences in the effects of dugs are often related to the difference in the rate of drug metabolisms (1,(8)(9)(10)(11).It is well known that there are marked individual differences in the effects of various drugs in animal and clinical experiments. On the other hand, it has been considered that such individual differences may be due to differences in the sensitivity of the target organs. However, there are no direct evidence for supporting such opinion on the basis of the drug level in the target organs. The present study, therefore, is designed to determine whether the individual differences in the effects of pentobarbital and zoxanolamine are correlated to the difference in the sensitivity or in the drug level of the target organ. METHODSFemale rats of Wistar strain, weighing about 180-200 g, were used. Pentobarbital sodium was dissolved in distilled water and zoxazolamine was suspended in 0.5% carboxy methylcellulose solution. The drugs were given intraperitoneally in volume of 2 ml/kg. Experimental schedule A) One-hundred seventy-eight rats were treated with pentobarbital soduim (30 mg/kg, i.p.) or zoxazolamine (110 mg/kg, i.p.). They were killed by exsanguination at the end of narcosis or paralysis and the concentration of drugs in the serum and brain was determined. The loss of righting reflex was used as the criteria of narcosis or paralysis.B) Eighty-one rats were numbered and treated with pentobarbital sodium (22 mg/ kg, i.p.) or zoxazolamine (85 mg/kg, i.p.) and were divided according to the degree of narcosis or paralysis. Fifteen or thirty minutes after the drug administration they were killed for the determination of the concentration of drugs in the serum and brain.

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“…It has been reported that species and sex differences in the effects of dugs are often related to the difference in the rate of drug metabolisms (1,(8)(9)(10)(11).…”

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Individual Difference in the Effect of Drugs in Relation to the Tissue Concentration of Drugs

Kato

Takanaka

Onoda

1969

Japanese Journal of Pharmacology

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“…An influence of sex differences on the disposition of drugs has been reported (Kato et al, 1962;Roberts et al, 1979;Trnavska & Trnavsky, 1983). The nature and degree of this influence is dependent on both the species and the drug under study.…”

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Influence of menstrual cycle on antipyrine pharmacokinetics in healthy Indian female volunteers.

Desai

et al. 1988

Brit J Clinical Pharma

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The effect of the menstrual cycle on antipyrine pharmacokinetics was studied in 11 normal, healthy Indian female volunteers. Antipyrine half‐ life, apparent volume of distribution, clearance and AUC were calculated by standard methods. Results indicated that in females, antipyrine half‐life was significantly longer on day 5 as compared with that on days 15 and 21 of the menstrual cycle. It appears that hormonal changes during the menstrual cycle affect the pharmacokinetics of drugs in normal healthy females.

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“…It was recently demonstrated that the activities of drug-metabolizing enzymes are an important factor for controling the action and toxicity of drugs (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

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“…The activities of drug metabolizing enzymes were altered by several factors, such as administration of some drugs, anabolic hormone, alloxan diabetes, hyperthyroidism and starvation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

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Effect of Starvation on the in Vivo Metabolism and Effect of Drugs in Female and Male Rats

Kato

Takanaka

1967

Jpn.J.Pharmacol

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The enzymes which metabolize lipid soluble compounds are localized in microsomes of liver and reduced NADP and molecular oxygen are required as cofactors. It was recently demonstrated that the activities of drug-metabolizing enzymes are an important factor for controling the action and toxicity of drugs (1-9).The activities of drug metabolizing enzymes were altered by several factors, such as administration of some drugs, anabolic hormone, alloxan diabetes, hyperthyroidism and starvation (1-15).1 n previous papers, it was reported that the activity of drug-metabolizing enzymes of liver microsomes in male rats was markedly decreased by starvation, while the activity i n female rats was increased (14).The starvation caused a decrease in liver weight as well as body weight and the blood flow of liver. On the other hand, studies on electron microscopy showed that endoplasmic reticulum in liver of fasted rats was markedly altered in their fine structure by starvation (16,17). Moreover, it has been considered that microsomes are artifacts during the homo genization of liver and they are likely derived from the endoplasmic reticulum. Thus, there is a possibility that the alternations in the enzyme activities in female and male rats may be artifacts during the homogenization.The purpose of the present investigation is to establish the correlation between the in vivo metabolism and activity of drugs and the in vitro metabolism of drugs in fasted female and male rats. METHODSFemale and male rats of \Vistar strain, weighing about 160 g and 180 g, respectively, were used. The rats were fasted for 2 days before the experiments.The estimation of drug ejects: The durations of pentobarbital narcosis, hexobarbital narcosis and zoxazolamine paralysis were measured by the duration of loss of righting reflex. Strychnine toxicity was determined by the percentage of convulsion and mortality. Toxi city of OMPA (Octamethylpyrophosphoramide) was determined by the median time of the onset of symptom, convulsion and death.

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Influence of sex difference on the pharmacological action and metabolism of some drugs

Cited by 120 publications

References 5 publications

Individual Difference in the Effect of Drugs in Relation to the Tissue Concentration of Drugs

Individual Difference in the Effect of Drugs in Relation to the Tissue Concentration of Drugs

Influence of menstrual cycle on antipyrine pharmacokinetics in healthy Indian female volunteers.

Effect of Starvation on the in Vivo Metabolism and Effect of Drugs in Female and Male Rats

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