Shenfield G M
Department of Clinical Pharmacology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Drug Saf. 1993 Jul;9(1):21-37. doi: 10.2165/00002018-199309010-00003.
There is a large quantity of literature on drug interactions with oral contraceptive (OC) steroids although their incidence is not known. The potential clinical significance of some interactions makes it important for all prescribing doctors and dentists to have some knowledge of the topic. Interactions may be divided into those in which OC effectiveness is impaired, causing breakthrough bleeding or pregnancy, those in which OC activity is enhanced by other drugs and those in which OCs interfere with the metabolism or activity of other therapeutic agents. Consideration of their pharmacology indicates that impairment of OC effect is most likely to be due to interference with ethinylestradiol. This is because this compound is sulphated in the gut wall, hydroxylated and glucuronidated in the liver, and undergoes enterohepatic recirculation. The progestogens are only metabolised in the liver and have no significant enterohepatic recirculation. Protein binding interactions are rarely of clinical importance. OC plasma concentrations may be reduced by induction of hepatic metabolism in the case of griseofulvin, rifampicin (rifampin) and several anticonvulsant drugs; valproic acid (sodium valproate) does not have this effect. Antibiotics may interfere with enterohepatic recirculation of ethinylestradiol and reduce plasma levels of active hormone. This is probably only of significance in a subgroup of women who may sometimes be suspected on history, but cannot be identified by any diagnostic test. Reasons for differences between case reports and formal studies of interactions with antibiotics are discussed. Plasma concentrations of ethinylestradiol may be increased by ascorbic acid (vitamin C) and paracetamol (acetaminophen) which compete with it for sulphation in the gut wall. Theoretically, problems may arise if these agents are stopped suddenly. Imidazole antifungal agents can inhibit ethinylestradiol metabolism and increase its plasma concentrations but the clinical significance of this is unknown. OCs have been shown to inhibit metabolism of many therapeutic drugs and increase their plasma concentrations. This may be of clinical significance in the case of benzodiazepines which are hydroxylated in the liver, but clinical effects are less certain with the other agents. OCs may induce metabolism of other drugs which are glucuronidated, including some benzodiazepines and analgesics. The clinical significance of this type of interaction is also unknown. It is suggested that all prescribers should remember to ask about OCs when taking a drug history and to consider the possibility of interactions with other drugs.
关于药物与口服避孕药（OC）甾体激素的相互作用，已有大量文献报道，尽管其发生率尚不清楚。某些相互作用的潜在临床意义使得所有开处方的医生和牙医了解这一主题非常重要。相互作用可分为以下几类：损害OC有效性，导致突破性出血或妊娠；其他药物增强OC活性；OC干扰其他治疗药物的代谢或活性。对其药理学的研究表明，OC效果受损最可能是由于对炔雌醇的干扰。这是因为该化合物在肠壁中硫酸化，在肝脏中羟基化和葡萄糖醛酸化，并经历肝肠循环。孕激素仅在肝脏中代谢，没有明显的肝肠循环。蛋白质结合相互作用在临床上很少具有重要意义。在灰黄霉素、利福平（利福霉素）和几种抗惊厥药物的情况下，肝脏代谢的诱导可能会降低OC的血浆浓度；丙戊酸（丙戊酸钠）没有这种作用。抗生素可能会干扰炔雌醇的肝肠循环并降低活性激素的血浆水平。这可能仅在一部分女性中具有重要意义，这些女性有时根据病史可能会被怀疑，但无法通过任何诊断测试来确定。讨论了病例报告与抗生素相互作用的正式研究之间差异的原因。炔雌醇的血浆浓度可能会因抗坏血酸（维生素C）和对乙酰氨基酚（扑热息痛）而增加，它们在肠壁中与炔雌醇竞争硫酸化。理论上，如果突然停用这些药物可能会出现问题。咪唑类抗真菌药物可以抑制炔雌醇的代谢并增加其血浆浓度，但其临床意义尚不清楚。已证明OC会抑制许多治疗药物的代谢并增加其血浆浓度。对于在肝脏中羟基化的苯二氮䓬类药物，这可能具有临床意义，但对于其他药物，临床效果不太确定。OC可能会诱导其他葡萄糖醛酸化药物的代谢，包括一些苯二氮䓬类药物和镇痛药。这种相互作用类型的临床意义也尚不清楚。建议所有开处方的医生在询问用药史时应记得询问OC，并考虑与其他药物相互作用的可能性。
