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关于体内生物利用度研究，FDA要说的和你要做的都在碗里啦！(a)Guidingprinciples.（a）指导原则(1)Thebasicprincipleinaninvivobioavailabilitystudyisthatnounnecessaryhumanresearchshouldbedone.（1）体内生物利用度研究的基本原理是无需进行不必要的人体研究。(2)Aninvivobioavailabilitystudyisgenerallydoneinanormaladultpopulationunderstandardizedconditions.Insomesituations,aninvivobioavailabilitystudyinhumansmaypreferablyandmoreproperlybedoneinsuitablepatients.Criticallyillpatientsshallnotbeincludedinaninvivobioavailabilitystudyunlesstheattendingphysiciandeterminesthatthereisapotentialbenefittothepatient.（2）通常在标准情况下于健康成年人群中进行体内生物利用度研究。在某些情况下，可以选择在合适的患者中进行体内生物利用度研究。不得将危重病人纳入体内生物利用度研究，除非主治医师确认参与的体内生物利用度试验对患者有潜在好处。(b)Basicdesign.Thebasicdesignofaninvivobioavailabilitystudyisdeterminedbythefollowing:（b）体内生物利用度研究的基本设计如下：(1)Thescientificquestionstobeanswered.（1）要回答的科学问题(2)Thenatureofthereferencematerialandthedosageformtobetested.（2）参比制剂和受试制剂的性质(3)Theavailabilityofanalyticalmethods.（3）分析方法的有效性(4)Benefit-riskconsiderationsinregardtotestinginhumans.（4）在人体中进行的试验要考虑利益-风险(c)Comparisontoareferencematerial.Invivobioavailabilitytestingofadrugproductshallbeincomparisontoanappropriatereferencematerialunlesssomeotherapproachismoreappropriateforvalidscientificreasons.（c）与参比制剂的比较。进行体内生物利用度的受试制剂应与适当的参比制剂比较，除非有其他更适合的有效的科学方法。(d)Previouslyunmarketedactivedrugingredientsortherapeuticmoieties.（d）先前未上市的药物活性成分或治疗结构(1)Aninvivobioavailabilitystudyinvolvingadrugproductcontaininganactivedrugingredientortherapeuticmoietythathasnotbeenapprovedformarketingcanbeusedtomeasurethefollowingpharmacokineticdata:（1）涉及含有未获批上市的药物活性成分或治疗结构的药物的体内生物利用度研究可通过检测如下药代动力学数据：(i)Thebioavailabilityoftheformulationproposedformarketing;and（i）计划上市的制剂的生物利用度；(ii)Theessentialpharmacokineticcharacteristicsoftheactivedrugingredientortherapeuticmoiety,suchastherateofabsorption,theextentofabsorption,thehalf-lifeofthetherapeuticmoietyinvivo,andtherateofexcretionand/ormetabolism.Doseproportionalityoftheactivedrugingredientorthetherapeuticmoietyneedstobeestablishedaftersingle-doseadministrationandincertaininstancesaftermultiple-doseadministration.Thischaracterizationisanecessarypartoftheinvestigationofthedrugtosupportdruglabeling.（ii）药物活性成分或治疗结构的基本药代动力学特征，例如吸收速率、吸收程度、体内治疗部位的半衰期以及排泄和/或代谢速率。需建立药物活性成分或治疗结构经单剂量给药多剂量给药后某些情况下的剂量比例。这是支持药品标签的药物研究的必要部分。(2)Thereferencematerialinsuchabioavailabilitystudyshouldbeasolutionorsuspensioncontainingthesamequantityoftheactivedrugingredientortherapeuticmoietyastheformulationproposedformarketing.（2）在此生物利用度研究中的参比制剂应该是溶液剂或者混悬液，而且要求含有与计划上市受试制剂等量的药物活性成分或治疗结构。(3)Thereferencematerialshouldbeadministeredbythesamerouteastheformulationproposedformarketingunlessanalternativeoradditionalrouteisnecessarytoanswerthescientificquestionunderstudy.Forexample,inthecaseofanactivedrugingredientortherapeuticmoietythatispoorlyabsorbedafteroraladministration,itmaybenecessarytocomparetheoraldosageformproposedformarketingwiththeactivedrugingredientortherapeuticmoietyadministeredinsolutionbothorallyandintravenously.（3）参比制剂应与受试制剂具有相同的给药途径，除非需其它给药途径可证明该项研究的科学性问题。例如，经口服给药后不宜吸收的药物活性成分或结构，则有必要将被计划上市的受试制剂的口服剂型与该药的口服和静脉滴注的溶液进行比较。(e)Newformulationsofactivedrugingredientsortherapeuticmoietiesapprovedformarketing.（e）药物活性成分或治疗结构的新制剂的获批上市：(1)Aninvivobioavailabilitystudyinvolvingadrugproductthatisanewdosageform,oranewsaltoresterofanactivedrugingredientortherapeuticmoietythathasbeenapprovedformarketingcanbeusedto:（1）体内生物利用度的研究包括已获准上市药物的新剂型，或药物活性成分或治疗结构的盐或酯：(i)Measurethebioavailabilityofthenewformulation,newdosageform,ornewsaltoresterrelativetoanappropriatereferencematerial;and（i）相对适当的参比制剂，测定新处方、新剂型或新盐或酯的生物利用度；(ii)Definethepharmacokineticparametersofthenewformulation,newdosageform,ornewsaltorestertoestablishdosagerecommendation.（ii）明确新制剂、新剂型或新盐或酯的药代动力学参数和推荐剂量。(2)Theselectionofthereferencematerial(s)insuchabioavailabilitystudydependsuponthescientificquestionstobeanswered,thedataneededtoestablishcomparabilitytoacurrentlymarketeddrugproduct,andthedataneededtoestablishdosagerecommendations.（2）在该生物利用度研究中要依据所要回答的科学问题来选择参比制剂，研究数据需要与市售药品建立可比性并且确定建议剂量。(3)Thereferencematerialshouldbetakenfromacurrentbatchofadrugproductthatisthesubjectofanapprovednewdrugapplicationandthatcontainsthesameactivedrugingredientortherapeuticmoiety,ifthenewformulation,newdosageform,ornewsaltoresterisintendedtobecomparabletoortomeetanycomparativelabelingclaimsmadeinrelationtothedrugproductthatisthesubjectofanapprovednewdrugapplication.（3）如果新处方、新剂型或新盐或酯想要与目前批准许可新药的标签要求具有可比性或者能与其媲美。那么参比制剂应选用目标批准许可新药的当前批次且含有相同的活性成分和治疗结构的产品。(f)Extendedreleaseformulations.（f）缓释制剂(1)Thepurposeofaninvivobioavailabilitystudyinvolvingadrugproductforwhichanextendedreleaseclaimismadeistodetermineifallofthefollowingconditionsaremet:(1)进行体内生物利用度研究的目的是为了确定缓释行为是否满足以下所有条件：(i)Thedrugproductmeetstheextendedreleaseclaimsmadeforit.（i）药品符合延缓释放的要求(ii)Thebioavailabilityprofileestablishedforthedrugproductrulesouttheoccurrenceofanydosedumping.（ii）为药品设定的生物利用度特性排除任何剂量倾泻行为的发生(iii)Thedrugproduct'ssteady-stateperformanceisequivalenttoacurrentlymarketednonextendedreleaseorextendedreleasedrugproductthatcontainsthesameactivedrugingredientortherape