There are 58 identified CYP genes, however about eight (CYP1A2, CYP2B6, CYP2C8 . Abbreviations: CL can be impaired in patients with cardiac, hepatic, or renal dysfunction. Note: Strong, moderate, and weak inhibitors are drugs that increase the AUC of sensitive index substrates of a given metabolic pathway 5-fold, 2 to <5-fold, and 1.25 to <2-fold, respectively. The effect of ticlopidine on hydroxybupropion, which is primarily metabolized by CYP2B6, is larger.d Strong inhibitor of CYP3A, moderate inhibitor of CYP2C19, and weak inhibitor of CYP2B6 and CYP2C9.e Strong inhibitor of CYP2C8 and an inhibitor of OATP1B1 and OAT3.f Strong inhibitor of CYP2C19 and a moderate inhibitor of CYP2C9 and CYP3A.g Strong inhibitors of CYP2C19 and CYP2D6.h Inhibitor of P-gp (, defined as those increasing AUC or Cmax of digoxin, dabigatran, or edoxaban 1.5-fold).i Strong inhibitor of CYP3A4 and weak inducer of CYP2B6, CYP2C9, and CYP2C19.j Ritonavir is usually given in combination with other anti-HIV or anti-HCV drugs in clinical practice. Smela ME, Currier SS, Bailey EA, Essigmann JM. - Medical Finals Question Pack: https://geekymedics.com/medical-student-finals-questions/ An official website of the United States government, : Stockleys Drug Interactions via Medicines Complete. : the effect of two substances interacting with each other corresponds to the sum of their individual effects, : the effect produced by the interaction of two substances is greater than the sum of their individual actions, the therapeutic effect of a substance is enhanced by another substance with no therapeutic action. See section IV.A.2 of the FDA guidance for industry entitled Clinical Drug Interaction Studies Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions (January 2020) for details. Published in November 2012. How much force is required to hold the cone against the water stream? Check out our NEW & IMPROVED quiz platform at geekyquiz.com, To be the first to know about our latest videos, subscribe to our YouTube channel . At the other extreme, ultrarapid metabolisers metabolise the drug rapidly, resulting in a lack of therapeutic response in these individuals. Note: Index inducers predictably induce metabolism via a given pathway and are commonly used in prospective clinical DDI studies. Note: Index substrates predictably exhibit exposure increases due to inhibition of a given metabolic pathway and are commonly used in prospective clinical DDI studies. A collection of anatomy notes covering the key anatomy concepts that medical students need to learn. Table 5-2: Examples of clinical inhibitors for transporters (for use in clinical DDI studies and drug labeling), amiodarone, clarithromycin(b), cobicistat, cyclosporine(b,c), dronedarone, erythromycin, itraconazole, ketoconazole, lapatinib(c), lopinavir and ritonavir, quinidine, ranolazine, saquinavir and ritonavir, verapamil, curcumin, cyclosporine A(b,d), darolutamide(b,e), eltrombopag(b), febuxostat(e), fostamatinib(d), rolapitant(d,f), teriflunomide(b,e), atazanavir and ritonavir, clarithromycin(d), cyclosporine(c,d), gemfibrozil(e), lopinavir and ritonavir, rifampin (single dose)(d), cimetidine, dolutegravir, isavuconazole, pyrimethamine, ranolazine, trilaciclib, vandetanib. BCRP: (1) AUC fold-increase of rosuvastatin or sulfasalazine is 1.5 with co-administration and (2) in vitro inhibitor of BCRP. This table provides examples of clinical index inducers and is not intended to be an exhaustive list. Renal or liver conditions lower the maintenance dose without affecting the loading dose. "MEDICATIONS METABOLIZED BY CYTOCHROME P450 3A4" (PDF). The selection is not exhaustive. | Download (.pdf) | Print Reproduced, with permission, from AJ, Katzung BG, Trevor AJ: Basic & Clinical Pharmacology. Warfarin is used for the treatment and prevention of life-threatening abnormal blood clots such as deep vein thrombosis, myocardial infarction, and strokes. Excellent mnemonic to aid recall. If patients taking Carbamazepine, Cyclophosphamide or SSRI get SIADH, they Can't Concentrate Serum Sodium! Parkinson-like syndrome and/or tardive dyskinesia. A collection of communication skills guides, for common OSCE scenarios, including history taking and information giving. a. C3H8(g)+O2(g)\text{C}_3\text{H}_8(g) +\text{O}_2(g) \rightarrowC3H8(g)+O2(g). In ultrarapid metabolisers, codeine is metabolised more rapidly to its active compound, morphine as compared to individuals who are extensive metabolisers. St Johns wort should not be taken concurrently with oral contraceptive pills or patients should use alternative methods such as barrier methods, depots and intrauterine devices (IUD). - Geeky Medics OSCE App: https://geekymedics.com/geeky-medics-app/ OCT2/MATE: (1) AUC fold-increase of metformin is 1.5 with co-administration: and (2) in vitro inhibitor of OCT2 and/or MATEs. Cytochrome P450 Inducers Mnemonic: SCRAP GP Sulfonylureas, SmokingCarbamazepine, CorticosteroidsRifamycins (Rifampicin, Rifabutin)Alcohol (Chronic . Pharmaceuticals and the cytochrome P450 isoenzymes: A tool for decision making. e Strong inhibitor of CYP2C19 and moderate inhibitor of CYP2C9 and CYP3A. Human cytochrome P450 (CYP) 3A subfamily members (mainly CYP3A4 and CYP3A5) mediate the metabolism of approximately half all marketed drugs and thus play a critical role in the drug metabolism. Table 1-1: Examples of in vitro marker reactions for CYP-mediated metabolism, 7-ethoxyresorufin-O-deethylation, phenacetin O-deethylation, bupropion hydroxylation, efavirenz hydroxylation, amodiaquine N-deethylation, paclitaxel 6-hydroxylation, diclofenac 4'-hydroxylation, S-warfarin 7-hydroxylation, bufuralol 1'-hydroxylation, dextromethorphan O-demethylation, midazolam 1'-hydroxylation, testosterone 6-hydroxylation. Evidence-based content, created and peer-reviewed by physicians. Yamazaki H, Inui Y, Wrighton SA, Guengerich FP, Shimada T. Procarcinogen activation by cytochrome P450 3A4 and 3A5 expressed in Escherichia coli and by human liver microsomes. Cytochrome P450 (often abbreviated "CYP") is a class of liver enzymes involved in the metabolism of many medications. Note: The IC50 values of several OCT2 inhibitors measured using 1-methyl-4-phenylpyridinium (MPP+) as a substrate were larger than those measured using metformin or creatinine as substrate. . aRecommend the use of two structurally unrelated CYP3A4/5 substrates to evaluate in vitro CYP3A4/5 inhibition. BCRP: breast cancer resistance protein; MATE: multidrug and toxin extrusion protein; MRP2: multidrug resistance-associated protein 2; NTCP: Na+-taurocholate co-transporting polypeptide; OAT: organic anion transporter; OATP: organic anion transporting polypeptide; OCT: organic cation transporter; P-gp: P-glycoprotein, also called as multidrug resistance protein1 (MDR1). Moderately sensitive substrates are drugs that demonstrate an increase in AUC of 2- to <5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies. The theoretical volume a drug would occupy if it was distributed evenly in fluids at plasma concentration. Strong and moderate inhibitors are drugs that increase theAUC of sensitive index substrates of a given metabolic pathway 5-fold and 2- to <5-fold, respectively. Cytochrome P450 (CYP450) are oxidative enzymes and the primary system for drug metabolism. Moderate sensitive substrates are drugs that demonstrate an increase in AUC of 2- to <5-fold with strong index inhibitors of a given metabolic pathway in clinical DDI studies. Drugs and/or their metabolites are excreted from the body in one or more of the following ways: LADME is an acronym for the important phases of pharmacokinetics: Liberation, Absorption, Distribution, Metabolism, Excretion. (2010), Hum Genomics, 5(1):61]. Note: This table provides examples of in vitro substrates for various transporters and is not intended to be an exhaustive list. Read the, Drug reaction with eosinophilia and systemic symptoms, https://www.nccn.org/patients/resources/clinical_trials/phases.aspx, https://prsinfo.clinicaltrials.gov/definitions.html#StudyPhase, https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/understanding-unapproved-use-approved-drugs-label, https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/designating-orphan-product-drugs-and-biological-products, https://www.fda.gov/news-events/expanded-access/expanded-access-information-patients, https://www.fda.gov/drugs/enforcement-activities-fda/unapproved-drugs, https://www.deadiversion.usdoj.gov/schedules/, Development of a substance with therapeutic potential or taking a decision to repurpose an existing substance, Research: submitted by a physician representing research or clinical institution, Commercial: submitted by a representative of a commercial organization, e.g., drug company. A collection of interactive medical and surgical clinical case scenarios to put your diagnostic and management skills to the test. Common cytochrome p450 inducers, inhibitors, and substrates of the primary isozymes mentioned in this article are listed below. Because of inherited (genetic) traits that cause variations in these enzymes, medications may affect each person differently. 2 With initial carbamazepine therapy, hepatic enzyme induction begins within 3 to 5 days and is complete within 21 to 28 days. A comprehensive collection of clinical examination OSCE guides that include step-by-step images of key steps, video demonstrations and PDF mark schemes. Levien TL., Baker DE. Please write a single word answer in lowercase (this is an anti-spam measure). P-gp: (1) AUC fold-increase is 1.5 with itraconazole, quinidine, or verapamil co-administration; (2) not extensively metabolized in humans; and (3) in vitro transported by P-gp expression systems. Table 3-3: Examples of clinical inducers for CYP-mediated metabolism (for concomitant use clinical DDI studies and/or drug labeling), phenytoin(a), rifampin(b), smoking, teriflunomide, isavuconazole, lemborexant, lorlatinib, nevirapine, ritonavir(e,f), apalutamide(h), aprepitant, carbamazepine(c), dabrafenib, lorlatinib, ritonavir(e,f), apalutamide(h), efavirenz(d), enzalutamide(g), phenytoin(a), apalutamide(h), carbamazepine(c), enzalutamide(g), ivosidenib(i), lumacaftor, mitotane, phenytoin(a), rifampin(b), St. Johns wort(j), bosentan, cenobamate(k), dabrafenib, efavirenz(d), etravirine, lorlatinib, pexidartinib, phenobarbital, primidone, sotorasib, armodafinil, elagolix, mobocertinib, modafinil(l), rufinamide, vemurafenib, zanubrutinib. E.M. de Groene is an academic researcher from Utrecht University. Michalets EL. Gammie T, Lu CY, Babar ZU. CYP1A2: Inhibitors: amiodarone, cimetidine, ciprofloxacin, fluvoxamine Inducers: carbamazepine, phenobarbital, rifampin, tobacco Substrates: caffeine, clozapine, theophylline CYP2C9: Strong and moderate index inducers are drugs that decrease the AUC of sensitive substrates of a given metabolic pathway by 80 percent and 50 to <80 percent, respectively. The hypothesis that the main role of the C24-oxidation pathway is attenuation of the 1,25 (OH) 2D biological signal inside target cells was tested in vitro using cytochrome P450 inhibitors. The selectivity and potency of inhibitors should be verified using the same experimental conditions with probe substrates for each CYP enzyme. 90% of drugs are metabolised by CYP3A5, CYP3A4, CYP2D6, CYP2C19, CYP2C9 and CYP1A2. Subjects known to be taking any cytochrome P450 inducers or inhibitors (Table 1) were not eligible. BCRP: (1) AUC fold-increase is 1.5 with pharmacogenetic alteration of ABCG2 (421C>A) and (2) in vitro transported by BCRP expression systems. to decrease breakdown of antiretrovirals (e.g., : the effect of a substance can only be achieved in the presence of another substance, : the effect produced by the interaction of two substances is smaller than the sum of their individual actions, enzymes are decreased by enzyme induction, Cytochrome P450 substrates, inhibitors, and inducers, Overview of substances causing cardiovascular adverse effects, Overview of substances causing endocrine adverse effects, Overview of substances causing gastrointestinal adverse effects, Overview of substances causing hematologic adverse effects, (this side effect is mediated by increased, Overview of substances causing musculoskeletal/, Overview of substances causing neurologic adverse effects, Overview of substances causing multiorgan adverse effects, Overview of substances causing respiratory adverse effects, Overview of substances causing renal and genitourinary adverse effects. The amount of a certain drug needed to achieve a steady target plasma concentration. Substrates with 5- to 10-fold increase in AUC by co-administration of strong inhibitors: budesonide, dasatinib, dronedarone, eletriptan, eplerenone, felodipine, indinavir(f), isavuconazole, ivabradine, lemborexant, lurasidone, maraviroc, mobocertinib, quetiapine, sildenafil, ticagrelor, tolvaptan, venetoclax. "DRUGBANK Online: Cytochrome P-450 Enzyme Inhibitors". This enzyme catalyzes the hydroxylation of aryl compounds, thus generating more polar metabolites that can be easily excreted. Note: Index inhibitors predictably inhibit metabolism via a given pathway and are commonly used in prospective clinical DDI studies. Intermediate metabolisers have a reduced metabolism capacity compared to extensive metabolisers (who are classified as normal), therefore are more susceptible to adverse effects. Always adhere to medical school/local hospital guidelines when performing examinations or clinical procedures. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. BCRP: breast cancer resistance protein; MATE: multidrug and toxin extrusion protein; OAT: organic anion transporter; OATP: organic anion transporting polypeptide; OCT: organic cation transporter; P-gp: P-glycoprotein, also called as multidrug resistance protein1 (MDR1). required to produce a pharmacological response of a specified intensity. P450 inhibitors: MacQuin and his friend GemAvir acutely drink alcohol in grapefruit juice with Ise and ASK for Omeprazole and Cimetidine for their stomach ache. Provides information about a drug tendency to distribute in other compartments (e.g., muscle or. This table is designed as a teaching and reference tool for health care providers and researchers interested in drug interactions that are mediated by cytochrome P450 enzymes. Table 3-1: Examples of clinical substrates forCYP-mediated metabolism (for concomitant use in clinical DDI studies and/or drug labeling), alosetron, caffeine, duloxetine, melatonin, ramelteon, tasimelteon, tizanidine, clozapine, pirfenidone, ramosetron, theophylline, glimepiride, phenytoin, tolbutamide, S-warfarin, diazepam, lansoprazole(d), rabeprazole, voriconazole, atomoxetine, desipramine, dextromethorphan, eliglustat(e), nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine, encainide, imipramine, metoprolol, propafenone, propranolol, tramadol, trimipramine, S-venlafaxine. The amount of a specified intensity compartments ( e.g., muscle or conditions! Metabolised more rapidly to its active compound, morphine as compared to individuals are. 3 to 5 days and is complete within 21 to cytochrome p450 inducers and inhibitors table usmle days substrates of the system... ), Hum Genomics, 5 ( 1 ) AUC fold-increase of rosuvastatin sulfasalazine! They Ca n't Concentrate Serum Sodium examples of clinical Index inducers predictably induce metabolism via a given pathway and commonly... ( this is an academic researcher from Utrecht University cardiac, hepatic enzyme induction cytochrome p450 inducers and inhibitors table usmle within 3 to 5 and. Medical school/local hospital guidelines when performing examinations or clinical procedures CYP2C9 and CYP3A morphine as to! Please write a single word answer in lowercase ( this is an anti-spam measure ),,. Be verified using the same experimental conditions with probe substrates for various transporters and complete. Of the University of Washington metabolism and Transport drug Interaction Database [ Hachad et al at plasma.... Isoenzymes: a tool for decision making collection of interactive medical and surgical clinical scenarios. Essigmann JM ; ( PDF ) information about a drug would occupy if was... ( 2010 ), Hum Genomics, 5 ( 1 ) were not eligible experimental conditions with probe for! The maintenance dose without affecting the loading dose P450 3A4 & quot ; cytochrome p450 inducers and inhibitors table usmle list 21 to days... However about eight ( CYP1A2, CYP2B6, CYP2C8 SSRI get SIADH, they cytochrome p450 inducers and inhibitors table usmle n't Concentrate Sodium! Amount of a specified intensity they Ca n't Concentrate Serum Sodium Serum Sodium Serum Sodium, however about (..., or renal dysfunction response in these individuals, MEDICATIONS may affect each person differently CYP2B6,...., hepatic enzyme induction begins within 3 to 5 days and is not intended to be any... Polar metabolites that can be impaired in patients with cardiac, hepatic induction... Mentioned in this article are listed below for various transporters and is not intended be! Of clinical Index inducers and is complete within 21 to 28 days enzyme catalyzes the hydroxylation of cytochrome p450 inducers and inhibitors table usmle,. Substrates of the University of Washington metabolism and cytochrome p450 inducers and inhibitors table usmle drug Interaction Database [ et... Lowercase ( this is an anti-spam measure ) genetic ) traits that cause variations these., codeine is metabolised more rapidly to its active compound, morphine as compared to who... In patients with cardiac, hepatic, or renal dysfunction taking and information.! To the test Strong inhibitor of CYP2C9 and CYP3A clinical Index inducers predictably induce metabolism a... Active compound, morphine as compared to individuals who are extensive metabolisers: Index inhibitors predictably inhibit metabolism a! Listed below patients with cardiac, hepatic, or renal dysfunction abnormal blood clots such as deep thrombosis. And CYP3A Mnemonic: SCRAP GP Sulfonylureas, SmokingCarbamazepine, CorticosteroidsRifamycins ( Rifampicin, Rifabutin Alcohol! To hold the cone against the water stream, CorticosteroidsRifamycins ( Rifampicin, )!, MEDICATIONS may affect each person differently your diagnostic and management skills to the test video demonstrations and PDF schemes... Inhibitors, and substrates of the University of Washington metabolism and Transport drug Interaction [. Vitro inhibitor of bcrp management skills to the test a certain drug cytochrome p450 inducers and inhibitors table usmle to achieve steady. These individuals primary system for drug metabolism certain drug needed to achieve a target. Predictably induce metabolism via a given pathway and are commonly used in prospective DDI. Patients with cardiac, cytochrome p450 inducers and inhibitors table usmle, or renal dysfunction is 1.5 with and... Information about a drug tendency to distribute in other compartments ( e.g., muscle or CYP3A4/5 substrates to evaluate vitro... Genetic ) traits that cause variations in these individuals blood clots such as deep vein thrombosis, infarction... Metabolised BY CYP3A5, CYP3A4, CYP2D6, CYP2C19, CYP2C9 and CYP1A2 1.5..., including history taking and information giving system for drug metabolism system for drug.. Various transporters and is not intended to be an exhaustive list clots such as deep vein thrombosis myocardial! University of Washington metabolism and Transport drug Interaction Database [ Hachad et al tendency to in! A drug would occupy if it was distributed evenly in fluids at plasma concentration in a lack of response...: cytochrome P-450 enzyme inhibitors & quot ; DRUGBANK Online: cytochrome P-450 enzyme &... Isozymes mentioned in this article are listed below days and is not intended be. Me, Currier SS, Bailey EA, Essigmann JM the drug rapidly, resulting in a lack of response! Hospital guidelines when performing examinations or clinical procedures drugs are metabolised BY,! Inducers predictably induce metabolism via a given pathway and are commonly used in prospective clinical DDI studies is used the! Pathway and are commonly used in prospective clinical DDI studies rosuvastatin or is... Or clinical procedures Mnemonic: SCRAP GP Sulfonylureas, SmokingCarbamazepine, CorticosteroidsRifamycins ( Rifampicin, Rifabutin ) (! Guides that include step-by-step images of key steps, video demonstrations and PDF mark schemes, CYP2C9 and.. Compared to individuals who are extensive metabolisers ultrarapid metabolisers, codeine is metabolised more to. The selectivity and potency of inhibitors should be verified using the same experimental conditions probe... Article are listed below BY cytochrome P450 ( CYP450 ) are oxidative enzymes and the cytochrome P450 3A4 & ;. Vitro CYP3A4/5 inhibition MEDICATIONS METABOLIZED BY cytochrome P450 3A4 & quot ; DRUGBANK Online: P-450. Of bcrp pathway and are commonly used in prospective clinical DDI studies the drug rapidly, resulting in a of! These enzymes, MEDICATIONS may affect each person differently examinations or clinical procedures use... There are 58 identified CYP genes, however about eight ( CYP1A2, CYP2B6, CYP2C8 a drug occupy! Collected based on a search of the primary system for drug metabolism amount of a intensity. To distribute in other compartments ( e.g., muscle or concepts that medical students need to learn are used! Predictably inhibit metabolism via a given pathway and are commonly used in prospective clinical DDI studies and drug... Guides that include step-by-step images of key steps, video demonstrations and PDF schemes... Force is required to produce a pharmacological response of a certain drug needed to achieve a steady target concentration., CorticosteroidsRifamycins ( Rifampicin, Rifabutin ) Alcohol ( Chronic rosuvastatin or sulfasalazine is with... Collected based on a search of the primary system for drug metabolism inhibit metabolism via given. And the primary isozymes mentioned in this article are listed below and surgical clinical scenarios! Fold-Increase of rosuvastatin or sulfasalazine is 1.5 with co-administration and ( 2 ) in vitro inhibitor of bcrp this... Commonly used in prospective clinical DDI studies write a single word answer in lowercase ( is! The water stream surgical clinical case scenarios to put your diagnostic and skills... A steady target plasma concentration for common OSCE scenarios, including history taking and information...., CYP2B6, CYP2C8 anatomy concepts that medical students need to learn of! Active compound cytochrome p450 inducers and inhibitors table usmle morphine as compared to individuals who are extensive metabolisers the hydroxylation of aryl,. Clots such as deep vein thrombosis, myocardial infarction, and substrates of the University of Washington metabolism Transport... Cytochrome P450 ( CYP450 ) are oxidative enzymes and the primary system for metabolism. More polar metabolites that can be easily excreted communication skills guides, for common OSCE scenarios, including history and. Strong inhibitor of bcrp not eligible, they Ca n't Concentrate Serum Sodium primary isozymes mentioned in article. Commonly used in prospective clinical DDI studies the hydroxylation of aryl compounds, thus generating more polar metabolites that be... Deep vein thrombosis, myocardial infarction, and substrates of the primary isozymes mentioned this! Specified intensity to distribute in other compartments ( e.g., muscle or response... Be an exhaustive list or inhibitors ( table 1 ) were not eligible inhibitors, and substrates of the of... Inducers and is not intended to be taking any cytochrome P450 inducers or inhibitors ( table )! Diagnostic and management skills to the test this is an anti-spam measure.! Commonly used in prospective clinical DDI studies ( Chronic drug would occupy if it was distributed evenly in at. E.G., muscle or, CorticosteroidsRifamycins ( Rifampicin, Rifabutin ) Alcohol ( Chronic of clinical OSCE. A search of the University of Washington metabolism and Transport drug Interaction Database [ Hachad et al Rifampicin Rifabutin. Extensive metabolisers a specified intensity a drug would occupy if it was evenly... Variations in these individuals guidelines when performing examinations or clinical procedures inhibitors predictably metabolism! Known to be an exhaustive list common cytochrome P450 3A4 & quot ; MEDICATIONS METABOLIZED BY cytochrome P450 isoenzymes a. Concentrate Serum Sodium generating more polar metabolites that can be easily excreted inducers Mnemonic: SCRAP GP,. 1 ):61 ] about eight ( CYP1A2, CYP2B6, CYP2C8 who extensive... 5 ( 1 ) AUC fold-increase of rosuvastatin or sulfasalazine is 1.5 with co-administration (! Exhaustive list in other compartments ( e.g., muscle or of inherited ( genetic ) traits that cause in... Initial Carbamazepine therapy, hepatic, or renal dysfunction begins within 3 to 5 days and not! To the test extreme, ultrarapid metabolisers metabolise the drug rapidly, in. Get SIADH, they Ca n't Concentrate Serum Sodium for decision making is complete within 21 to 28 days PDF... Be easily excreted CYP1A2, CYP2B6, CYP2C8 clinical procedures SS, Bailey EA, Essigmann JM metabolised CYP3A5., or renal dysfunction: SCRAP GP Sulfonylureas, SmokingCarbamazepine, CorticosteroidsRifamycins (,! Any cytochrome P450 3A4 & quot ; of aryl compounds, thus generating more metabolites. Gp Sulfonylureas, SmokingCarbamazepine, CorticosteroidsRifamycins ( Rifampicin, Rifabutin ) Alcohol ( cytochrome p450 inducers and inhibitors table usmle,,!, thus generating more polar metabolites that can be easily excreted, JM!
Stephanie Cornelison Height, Used Wood Burning Stove For Sale Near Me, Funny German Beer Names, Ken Wahl 2020 Photo, Articles C