Duloxetine: clinical pharmacokinetics and drug interactions

Duloxetine, a potent reuptake inhibitor of serotonin (5-HT) and norepinephrine, is effective for the treatment of major depressive disorder, diabetic neuropathic pain, stress urinary incontinence, generalized anxiety disorder and fibromyalgia. Duloxetine achieves a maximum plasma concentration (C(max)) of approximately 47?ng/mL (40?mg twice-daily dosing) to 110?ng/mL (80?mg twice-daily dosing) approximately 6 hours after dosing. The elimination half-life of duloxetine is approximately 10-12 hours and the volume of distribution is approximately 1640?L. The goal of this paper is to provide a review of the literature on intrinsic and extrinsic factors that may impact the pharmacokinetics of duloxetine with a focus on concomitant medications and their clinical implications. Patient demographic characteristics found to influence the pharmacokinetics of duloxetine include sex, smoking status, age, ethnicity, cytochrome P450 (CYP) 2D6 genotype, hepatic function and renal function. Of these, only impaired hepatic function or severely impaired renal function warrant specific warnings or dose recommendations. Pharmacokinetic results from drug interaction studies show that activated charcoal decreases duloxetine exposure, and that CYP1A2 inhibition increases duloxetine exposure to a clinically significant degree. Specifically, following oral administration in the presence of fluvoxamine, the area under the plasma concentration-time curve and C(max) of duloxetine significantly increased by 460% (90% CI 359, 584) and 141% (90% CI 93, 200), respectively. In addition, smoking is associated with a 30% decrease in duloxetine concentration. The exposure of duloxetine with CYP2D6 inhibitors or in CYP2D6 poor metabolizers is increased to a lesser extent than that observed with CYP1A2 inhibition and does not require a dose adjustment. In addition, duloxetine increases the exposure of drugs that are metabolized by CYP2D6, but not CYP1A2. Pharmacodynamic study results indicate that duloxetine may enhance the effects of benzodiazepines, but not alcohol or warfarin. An increase in gastric pH produced by histamine H(2)-receptor antagonists or antacids did not impact the absorption of duloxetine. While duloxetine is generally well tolerated, it is important to be knowledgeable about the potential for pharmacokinetic interactions between duloxetine and drugs that inhibit CYP1A2 or drugs that are metabolized by CYP2D6 enzymes.     

Rabeprazole: pharmacokinetics and pharmacokinetic drug interactions

Rabeprazole is the most recently approved proton pump inhibitor in Germany. The substance has an absolute bioavailability upon oral administration of approximately 52% which is robust against food intake or administration of antacids. Maximal plasma concentrations are reached after approximately 3-4 h. Concentrations increase proportionally with the dose. Rabeprazole undergoes an almost complete, mainly non-enzymatic metabolism with renal elimination of the metabolites. CYP3A4 and CYP2C19 contribute to the fraction of metabolism mediated enzymatically. Elimination half-life is about 1 h. The extent of rabeprazole concentration increase by old age, poor metabolizer status for CYP2C19 and impairment of liver function is not greater than two-fold, impaired renal function does not affect the elimination. Even in patients with delayed elimination, no relevant accumulation of rabeprazole was observed upon long-term administration. In in vivo studies, rabeprazole had no noteworthy effect on the metabolism of other drugs. This statement however must be made with reservation because of shortcomings in published studies with respect to the methods used and presentation and because of lacking investigations about possible effects on the cytochrome P-450 enzymes CYP3A4 and CYP2D6. A slight reduction in ketoconazole absorption and a moderate increase in digoxin concentrations should be taken into account for concomitant therapy, but is expected to be clinically relevant only in isolated cases. Based on these partially incomplete data, in summary it is to be expected that rabeprazole can be administered at a standard dose for the respective disease in almost any patient for the entire duration of therapy, and that usually no dose adjustment of other drugs is required when rabeprazole is coadministered.     

Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and pharmacological interactions

The development of new "atypical" antipsychotic agents, which are safer than classical neuroleptics and also active against the negative symptoms and neurocognitive deficits caused by the illness, has produced a significant advancement in the treatment of schizophrenia. The atypical (or "second generation") antipsychotics have several therapeutical properties in common, however they can significantly differ with regard to clinical potency and side effects. The main features regarding pharmacodynamics, pharmacokinetics and pharmacological interactions of the most important atypical antipsychotics, namely clozapine, olanzapine, quetiapine and risperidone, are treated herein. Several analytical methods available for the therapeutic drug monitoring of these drugs are also presented, as well as the novel formulations, which can notably improve the therapy of schizophrenia. Other very recent atypical agents, such as ziprasidone, aripiprazole, iloperidone, sertindole and zotepine will also be briefly described.     

双膦酸盐类药物的药动学及药物相互作用研究进展

双膦酸盐类药物用于预防与治疗骨吸收相关疾病,包括第1代的依替膦酸二钠、替鲁膦酸二钠、氯膦酸二钠,第2代的帕米膦酸二钠、阿仑膦酸钠,第3代的利塞膦酸钠、伊班膦酸钠、唑来膦酸等。该类药物口服达峰时间较短,吸收率偏低,生物利用度很低;骨结合部分的半衰期较长,药物留存时间也较长。与双膦酸盐联用产生相互作用的药物主要为：含有二价阳离子药物、其他双膦酸盐药物、华法林、苯妥英、非甾体类抗炎药、抗癌药、激素、H2受体拮抗剂以及肾毒性药物。从药动学角度解释双膦酸的药物相互作用,以避免不良反应发生。     

Fomivirsen: clinical pharmacology and potential drug interactions

Fomivirsen sodium is a 21-base phosphorothioate oligodeoxynucleotide complementary to the messenger RNA of the major immediate-early region proteins of human cytomegalovirus, and is a potent and selective antiviral agent for cytomegalovirus retinitis. Following intravitreal administration, fomivirsen is slowly cleared from vitreous with a half-life of approximately 55 hours in humans. Preclinical studies show that fomivirsen distributes to retina and is slowly metabolised by exonuclease digestion. Clearance from retina was shown to be similarly slow following loading from the vitreous. The estimated half-life for clearance of fomivirsen from retina was 78 hours in monkeys following a 115-microg dose. Because of the low doses coupled with slow disposition from the eye, measurable concentrations of drug are not detected in the systemic circulation following intravitreal administration. Systemically administered phosphorothioate oligodeoxynucleotides are highly bound to albumin and alpha2-macroglobulin in blood plasma. Because fomivirsen does not compete for oxidative metabolic processes involved in clearance of many xenobiotics, the most likely mechanism for drug interactions may be altered protein binding of a coadministered drug. The extremely low systemic exposure to this oligodeoxynucleotide following intravitreal administration largely negates its potential ability to interact with systemically administered drugs. Even if fomivirsen were able to access the blood, protein binding assays indicate that drugs that are site I and site II binders of albumin (warfarin, ibuprofen, salicylic acid) are not displaced in the presence of phosphorothioate oligodeoxynucleotides of various sequences at concentrations orders of magnitude higher than that seen for fomivirsen. Administration of fomivirsen with numerous systemically administered antiretrovirals (for example zidovudine and zalcitabine) as well as systemically administered anticytomegalovirus agents such as foscarnet and ganciclovir has been reported to be well tolerated. The only reported warning is a recommendation against administration within 2 to 4 weeks of cidofovir treatment due to an increased risk of ocular inflammation.     

Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications

Oral mucosal drug delivery is an alternative method of systemic drug delivery that offers several advantages over both injectable and enteral methods. Because the oral mucosa is highly vascularised, drugs that are absorbed through the oral mucosa directly enter the systemic circulation, bypassing the gastrointestinal tract and first-pass metabolism in the liver. For some drugs, this results in rapid onset of action via a more comfortable and convenient delivery route than the intravenous route. Not all drugs, however, can be administered through the oral mucosa because of the characteristics of the oral mucosa and the physicochemical properties of the drug. Several cardiovascular drugs administered transmucosally have been studied extensively. Nitroglycerin is one of the most common drugs delivered through the oral mucosa. Research on other cardiovascular drugs, such as captopril, verapamil and propafenone, has proven promising. Oral transmucosal delivery of analgesics has received considerable attention. Oral transmucosal fentanyl is designed to deliver rapid analgesia for breakthrough pain, providing patients with a noninvasive, easy to use and nonintimidating option. For analgesics that are used to treat mild to moderate pain, rapid onset has relatively little benefit and oral mucosal delivery is a poor option. Oral mucosal delivery of sedatives such as midazolam, triazolam and etomidate has shown favourable results with clinical advantages over other routes of administration. Oral mucosal delivery of the antinausea drugs scopolamine and prochlorperazine has received some attention, as has oral mucosal delivery of drugs for erectile dysfunction. Oral transmucosal formulations of testosterone and estrogen have been developed. In clinical studies, sublingual testosterone has been shown to result in increases in lean muscle mass and muscle strength, improvement in positive mood parameters, and increases in genital responsiveness in women. Short-term administration of estrogen to menopausal women with cardiovascular disease has been shown to produce coronary and peripheral vasodilation, reduction of vascular resistance and improvement in endothelial function. Studies of sublingual administration of estrogen are needed to clarify the most beneficial regimen. Although many drugs have been evaluated for oral transmucosal delivery, few are commercially available. The clinical need for oral transmucosal delivery of a drug must be high enough to offset the high costs associated with developing this type of product. Drugs considered for oral transmucosal delivery are limited to existing products, and until there is a change in the selection and development process for new drugs, candidates for oral transmucosal delivery will be limited.     

Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions

Ezetimibe is the first lipid-lowering drug that inhibits intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients. Following oral administration, ezetimibe is rapidly absorbed and extensively metabolised (>80%) to the pharmacologically active ezetimibe-glucuronide. Total ezetimibe (sum of 'parent' ezetimibe plus ezetimibe-glucuronide) concentrations reach a maximum 1-2 hours post-administration, followed by enterohepatic recycling and slow elimination. The estimated terminal half-life of ezetimibe and ezetimibe-glucuronide is approximately 22 hours. Consistent with the elimination half-life of ezetimibe, an approximate 2-fold accumulation is observed upon repeated once-daily administration. The recommended dose of ezetimibe 10 mg/day can be administered in the morning or evening without regard to food. There are no clinically significant effects of age, sex or race on ezetimibe pharmacokinetics and no dosage adjustment is necessary in patients with mild hepatic impairment or mild-to-severe renal insufficiency. The major metabolic pathway for ezetimibe consists of glucuronidation of the 4-hydroxyphenyl group by uridine 5'-diphosphate-glucuronosyltransferase isoenzymes to form ezetimibe-glucuronide in the intestine and liver. Approximately 78% of the dose is excreted in the faeces predominantly as ezetimibe, with the balance found in the urine mainly as ezetimibe-glucuronide. Overall, ezetimibe has a favourable drug-drug interaction profile, as evidenced by the lack of clinically relevant interactions between ezetimibe and a variety of drugs commonly used in patients with hypercholesterolaemia. Ezetimibe does not have significant effects on plasma levels of HMG-CoA reductase inhibitors commonly known as statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin), fibric acid derivatives (gemfibrozil, fenofibrate), digoxin, glipizide, warfarin and triphasic oral contraceptives (ethinylestradiol and levonorgestrel). Concomitant administration of food, antacids, cimetidine or statins had no significant effect on ezetimibe bioavailability. Although coadministration with gemfibrozil and fenofibrate increased the bioavailability of ezetimibe, the clinical significance is thought to be minor considering the relatively flat dose-response curve of ezetimibe and the lack of dose-related increase in adverse events. In contrast, coadministration with the bile acid binding agent colestyramine significantly decreased ezetimibe oral bioavailability (based on area under the plasma concentration-time curve of total ezetimibe). Hence, ezetimibe and colestyramine should be administered several hours apart to avoid attenuating the efficacy of ezetimibe. Finally, higher ezetimibe exposures were observed in patients receiving concomitant ciclosporin, and ezetimibe caused a small but statistically significant effect on plasma levels of ciclosporin. Because treatment experience in patients receiving ciclosporin is limited, physicians are advised to exercise caution when initiating ezetimibe in the setting of ciclosporin coadministration, and to carefully monitor ciclosporin levels.     

中药甘草的药代动力学以及药物相互作用研究进展

甘草是最古老和最常用的中草药之一,药理作用多样且临床应用广泛,但甘草也会引起不良反应和药物相互作用,了解甘草的化学成分、体内处置以及潜在的药物相互作用,对于它的临床安全、合理使用具有重要意义。本文综述并讨论了近几十年来关于甘草的药代动力学以及药物相互作用研究,促进对甘草的全面认识,保证临床用药安全。     

ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions

Nine proteins of the ABC superfamily (P-glycoprotein, 7 MRPs and BCRP) are involved in multidrug transport. Being localised at the surface of endothelial or epithelial cells, they expel drugs back to the external medium (if located at the apical side [P-glycoprotein, BCRP, MRP2, MRP4 in the kidney]) or to the blood (if located at the basolateral side [MRP1, MRP3, MRP4, MRP5]), modulating thereby their absorption, distribution, and elimination. In the CNS, most transporters are oriented to expel drugs to the blood. Transporters also cooperate with Phase I/Phase II metabolism enzymes by eliminating drug metabolites. Their major features are (i) their capacity to recognize drugs belonging to unrelated pharmacological classes, and (ii) their redundancy, a single molecule being possibly substrate for different transporters. This ensures an efficient protection of the body against invasion by xenobiotics. Competition for transport is now characterized as a mechanism of interaction between co-administered drugs, one molecule limiting the transport of the other, potentially affecting bioavailability, distribution, and/or elimination. Again, this mechanism reinforces drug interactions mediated by cytochrome P450 inhibition, as many substrates of P-glycoprotein and CYP3A4 are common. Induction of the expression of genes coding for MDR transporters is another mechanism of drug interaction, which could affect all drug substrates of the up-regulated transporter. Overexpression of MDR transporters confers resistance to anticancer agents and other therapies. All together, these data justify why studying drug active transport should be part of the evaluation of new drugs, as recently recommended by the FDA.     

Thrombolytics: drug interactions of clinical significance.

Thrombolytic agents activate plasminogen and induce a systemic fibrinolytic and anticoagulant state. Interaction of fibrinolysis with coagulation and platelet aggregation might be important for synergistic interactions with other antiplatelet or anticoagulant drugs. Thrombolytic agents are most often used in patients with coexisting cardiovascular medication, including various antihypertensives, beta-blocking agents, nitrates and aspirin (acetylsalicylic acid). In acute coronary syndromes, anticoagulants and antiplatelet compounds such as clopidogrel or glycoprotein IIb/IIIa receptor antagonists might be given. Inducers or inhibitors of the cytochrome P450 system are not reported to affect the pharmacokinetics of any thrombolytic agent. Since the elimination of the recombinant plasminogen activators saruplase and alteplase is dependent on liver blood flow, drugs affecting hepatic blood flow could theoretically affect the hepatic clearance of these agents. In fact, a reduction in thrombolytic activity has only been demonstrated for alteplase with nitroglycerin (glyceryl trinitrate). Pharmacodynamic interactions occur more often. The additive and beneficial effect of aspirin as concomitant therapy to thrombolysis has been demonstrated without excessive bleeding rates. No data are available on the interaction between ticlopidine or clopidogrel and thrombolytic agents in humans. Anticoagulation by heparin concomitantly with thrombolysis improves the patency rate of the occluded coronary vessel, but bleeding complications are seen more frequently. Although there has been no controlled study on the interaction between oral anticoagulants and thrombolytic agents, patients with myocardial infarction who were taking an oral anticoagulant before admission seem to be at higher risk for intracranial haemorrhage during thrombolytic therapy. Currently, no recommendations can be given for possible dose adjustment of thrombolytic therapy in patients receiving antiplatelet comedication. For comedication with heparin, it has been advised to monitor activated partial thromboplastin time frequently and to avoid values >2.5-fold normal. Patients receiving thrombolytic treatment should be monitored frequently for bleeding and the physician should be aware of any comedication exerting antiplatelet (e.g. aspirin, clopidogrel and ticlopidine) or anticoagulant (e.g. warfarin) effects.     

Transporter-mediated drug interactions: clinical implications and in vitro assessment

Although they are less frequently compared with the reported cases of CYP-mediated drug interactions, clinically significant transporter-mediated drug interactions, which are mainly based on efflux transporter or P-glycoprotein data, have been reported. Unlike the CYP-mediated drug interactions that can be readily defined by inhibition or induction of CYP enzymes, the evidence for the so-called transporter-mediated drug interactions is often less conclusive. The difficulty in defining transporter-mediated drug interactions is due mainly to the interplay between transporters and drug-metabolizing enzymes in drug disposition, and the lack of specific and potent inhibitors for each transporter and enzyme. An important lesson learned from animal studies is that transporter inhibition has a much greater impact on the tissue distribution of drugs than on the systemic exposure of drugs measured in plasma. The potential risk of transporter-mediated drug interactions might be underestimated if only plasma concentrations are monitored.     

Influence of drug transport proteins on the pharmacokinetics and drug interactions of HIV protease inhibitors

Protease inhibitors, a class of antiretroviral agents frequently used in the treatment of HIV infection, interact with numerous transport proteins resulting in clinically significant drug-drug interactions (DDIs). This review focuses on the proteins that transport protease inhibitors and directly influence the pharmacokinetics of these drugs, as well as the transport proteins that are inhibited or induced by protease inhibitors. Clinically relevant DDIs involving drug transporters and protease inhibitors, either as "victim" drugs or as "perpetrator" drugs, and the pharmacokinetic consequences of such interactions are highlighted. A summary of transporter-mediated processes underlying the toxicity of protease inhibitors is provided. Finally, the effect of HIV infection or co-infection on drug transport proteins, and the implications for protease inhibitor pharmacokinetics is discussed. Transport proteins significantly influence the pharmacokinetics, efficacy and toxicity profiles of this important class of drugs.     

Antiarrhythmic agents: drug interactions of clinical significance.

The management of cardiac arrhythmias has grown more complex in recent years. Despite the recent focus on nonpharmacological therapy, most clinical arrhythmias are treated with existing antiarrhythmics. Because of the narrow therapeutic index of antiarrhythmic agents, potential drug interactions with other medications are of major clinical importance. As most antiarrhythmics are metabolised via the cytochrome P450 enzyme system, pharmacokinetic interactions constitute the majority of clinically significant interactions seen with these agents. Antiarrhythmics may be substrates, inducers or inhibitors of cytochrome P450 enzymes, and many of these metabolic interactions have been characterised. However, many potential interactions have not, and knowledge of how antiarrhythmic agents are metabolised by the cytochrome P450 enzyme system may allow clinicians to predict potential interactions. Drug interactions with Vaughn-Williams Class II (beta-blockers) and Class IV (calcium antagonists) agents have previously been reviewed and are not discussed here. Class I agents, which primarily block fast sodium channels and slow conduction velocity, include quinidine, procainamide, disopyramide, lidocaine (lignocaine), mexiletine, flecainide and propafenone. All of these agents except procainamide are metabolised via the cytochrome P450 system and are involved in a number of drug-drug interactions, including over 20 different interactions with quinidine. Quinidine has been observed to inhibit the metabolism of digoxin, tricyclic antidepressants and codeine. Furthermore, cimetidine, azole antifungals and calcium antagonists can significantly inhibit the metabolism of quinidine. Procainamide is excreted via active tubular secretion, which may be inhibited by cimetidine and trimethoprim. Other Class I agents may affect the disposition of warfarin, theophylline and tricyclic antidepressants. Many of these interactions can significantly affect efficacy and/or toxicity. Of the Class III antiarrhythmics, amiodarone is involved in a significant number of interactions since it is a potent inhibitor of several cytochrome P450 enzymes. It can significantly impair the metabolism of digoxin, theophylline and warfarin. Dosages of digoxin and warfarin should empirically be decreased by one-half when amiodarone therapy is added. In addition to pharmacokinetic interactions, many reports describe the use of antiarrhythmic drug combinations for the treatment of arrhythmias. By combining antiarrhythmic drugs and utilising additive electrophysiological/pharmacodynamic effects, antiarrhythmic efficacy may be improved and toxicity reduced. As medication regimens grow more complex with the aging population, knowledge of existing and potential drug-drug interactions becomes vital for clinicians to optimise drug therapy for every patient.     

瑞舒伐他汀药代动力学及与其他药物的相互作用研究进展

瑞舒伐他汀是新一代他汀类药物,相对之前的他汀类药物,肝选择性更好;肝代谢少、消除半衰期长,具有更强的降脂作用,临床应用前景广泛;其耐受性良好,不良反应发生率与同类其他药物相似。本文对瑞舒伐他汀的药代动力学及与其他药物相互作用作一综述。以期为指导瑞舒伐他汀的临床用药打下坚实的理论基础,确保临床用药的安全性和有效性,真正实现临床上的个体化给药。     

Antiepileptic drug interactions - principles and clinical implications

Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to drug interactions. The purpose of the present review is to focus upon clinically relevant interactions where AEDs are involved and especially on pharmacokinetic interactions. The older AEDs are susceptible to cause induction (carbamazepine, phenobarbital, phenytoin, primidone) or inhibition (valproic acid), resulting in a decrease or increase, respectively, in the serum concentration of other AEDs, as well as other drug classes (anticoagulants, oral contraceptives, antidepressants, antipsychotics, antimicrobal drugs, antineoplastic drugs, and immunosupressants). Conversely, the serum concentrations of AEDs may be increased by enzyme inhibitors among antidepressants and antipsychotics, antimicrobal drugs (as macrolides or isoniazid) and decreased by other mechanisms as induction, reduced absorption or excretion (as oral contraceptives, cimetidine, probenicid and antacides). Pharmacokinetic interactions involving newer AEDs include the enzyme inhibitors felbamate, rufinamide, and stiripentol and the inducers oxcarbazepine and topiramate. Lamotrigine is affected by these drugs, older AEDs and other drug classes as oral contraceptives. Individual AED interactions may be divided into three levels depending on the clinical consequences of alterations in serum concentrations. This approach may point to interactions of specific importance, although it should be implemented with caution, as it is not meant to oversimplify fact matters. Level 1 involves serious clinical consequences, and the combination should be avoided. Level 2 usually implies cautiousness and possible dosage adjustments, as the combination may not be possible to avoid. Level 3 refers to interactions where dosage adjustments are usually not necessary. Updated knowledge regarding drug interactions is important to predict the potential for harmful or lacking effects involving AEDs.     

Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as harmaline. Concurrent use of harmaline reduces 5-MeO-DMT deamination metabolism and leads to a prolonged and increased exposure to the parent drug 5-MeO-DMT, as well as the active metabolite bufotenine. Harmaline, 5-MeO-DMT and bufotenine act agonistically on serotonergic systems and may result in hyperserotonergic effects or serotonin toxicity. Interestingly, CYP2D6 also has important contribution to harmaline metabolism, and CYP2D6 genetic polymorphism may cause considerable variability in the metabolism, pharmacokinetics and dynamics of harmaline and its interaction with 5-MeO-DMT. Therefore, this review summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT. In addition, the pharmacokinetic and pharmacodynamic drug-drug interactions between harmaline and 5-MeO-DMT, potential involvement of CYP2D6 pharmacogenetics, and risks of 5-MeO-DMT intoxication are discussed.     

转运体介导的药物相互作用对药物吸收的影响及其临床意义

目前,临床实践中使用的大多数药物是经口服给药,必须经过充分和持续地吸收才能达到效果。药物吸收在口服药物治疗疾病中起着先决条件,其中药物转运体在药物的肠道吸收中起主要作用。同时药物的联合应用在临床上越来越普遍,通常通过使用多种药物来达到治疗效果,但联合用药大多会产生一定的药物相互作用,从而影响药物的药动学特点。综述肠道转运体介导的几类药物相互作用对其吸收的影响及临床意义,为临床应用提供参考。