Details of the Drug

General Information of Drug (ID: DMD5JU8)

• Drug Name: Cephalexin
• Synonyms: Adcadina; Ades[prex; Alcephin; Alexin; Alsporin; Ambal; Aristosporin; Azabort; Bactopenor; Beliam; Biocef; CEX; Carnosporin; Cefablan; Cefacet; Cefadal; Cefadin; Cefadina; Cefalekey; Cefaleksin; Cefalessina; Cefalexgobens; Cefalexin; Cefalexina; Cefalexine; Cefalexinum; Cefalin; Cefalival; Cefaloto; Cefaseptin; Cefax; Ceffanex; Cefibacter; Ceflax; Ceforal; Cefovit; Celexin; Cepastar; Cepexin; Cephacillin; Cephalexine; Cephalexinum; Cephalobene; Cephanasten; Cephaxin; Cephin; Cepol; Ceporex; Ceporexin; Ceporexine; Check; Cophalexin; Domucef; Doriman; Durantel; Efemida; Erocetin; Factagard; Felexin; Fexin; Ibilex; Ibrexin; Inphalex; Karilexina; Kefalospes; Keflet; Keflex; Kefolan; Keforal; Keftab; Kekrinal; Kidolex; Lafarine; Larixin; Lenocef; Lexibiotico; Loisine; Lonflex; Lopilexin; Losporal; Madlexin; Maksipor; Mamalexin; Mamlexin; Medolexin; Medoxine; Neokef; Neolexina; Noveol; Novolexin; Nufex; Oracef; Oriphex; Oroxin; Ortisporina; Ospexin; Palitrex; Pectril; Prindex; Pyassan; Rilexine; Roceph; Rogevil; Sanaxin; Sartosona; Sencephalin; Sepexin; Servicef; Servispor; Sialexin; Sinthecillin; Sintolexyn; Sporicef; Sporidex; Syncl; Syncle; Synecl; Tepaxin; Theratrex; Tokiolexin; Uphalexin; Viosporine; Voxxim; Winlex; Zabytrex; Zozarine; Cefalessina [DCIT]; Cefalexin Scand Pharm; Cefalexin Sodium; Cefalexin generics; Cefalexin hydrate; Cefalexin monohydrate; Cefalexina Northia; Cefalexina Richet; Cephalex von ct; Cephalexin hydrate; Cephalexin monohydrate; Ceporex Forte; Durantel DS; Henina Oral; Panixine Disperdose; Roceph Distab; Lilly 66873; S 6437; SQ 20248; Cefa-iskia; Cefalexin (JP15); Cefalexin.H2O; Cefalexina [INN-Spanish]; Cefalexine [INN-French]; Cefalexinum [INN-Latin]; Cephalexin(USP); Cephalexin (anhydrous); Cephalexin 1-hydrate; Cephalexin 1-wasser; Cephalexin [USAN:BAN]; Cephalexin.H2O; Ceporexin-E; Cusisporina-Cefalox; Ed A-Ceph; KS-1134; Keflex (TN); Keftab (TN); L-Keflex; Panixine disperdose (TN); Sporidex (TN); Cephalexin, (6R-(6alpha,7beta))-Isomer; 7-(D-2-Amino-2-phenylacetamido)-3-methyl-delta (sup 3)-cephem-4-carboxylic acid; 7-(D-2-Amino-2-phenylacetamido)-3-methyl-delta3-cephem-4-carboxylic acid; 7-(D-alpha-Aminophenylacetamido)desacetoxycephalosporanic acid

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1], [2]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 347.4
  Topological Polar Surface Area (xlogp); 0.6
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 31 mg/L [3]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.3 h [3]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
  Bioavailability: The bioavailability of drug is 100% [3]
  Clearance: The clearance of drug is 376 mL/min [5]
  Elimination: Cephalexin is over 90% excreted in the urine after 6 hours by glomerular filtration and tubular secretion with a mean urinary recovery of 99.3%. Cephalexin is unchanged in the urine [6]
  Half-life: The concentration or amount of drug in body reduced by one-half in 49.5 minutes [5]
  Metabolism: The drug is not metabolised [7]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 192.00014 micromolar/kg/day [8]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.85% [9]
  Vd: The volume of distribution (Vd) of drug is 5.2-5.8 L [10]
  Water Solubility: The ability of drug to dissolve in water is measured as 12 mg/mL [4]
• Chemical Identifiers:
  Formula: C16H17N3O4S
  IUPAC Name: (6R,7R)-7-[[(2R)-2-amino-2-phenylacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  Canonical SMILES: CC1=C(N2[C@@H]([C@@H](C2=O)NC(=O)[C@@H](C3=CC=CC=C3)N)SC1)C(=O)O
  InChI: InChI=1S/C16H17N3O4S/c1-8-7-24-15-11(14(21)19(15)12(8)16(22)23)18-13(20)10(17)9-5-3-2-4-6-9/h2-6,10-11,15H,7,17H2,1H3,(H,18,20)(H,22,23)/t10-,11-,15-/m1/s1
  InChIKey: ZAIPMKNFIOOWCQ-UEKVPHQBSA-N
• Cross-matching ID:
  PubChem CID: 27447
  ChEBI ID: CHEBI:3534
  CAS Number: 15686-71-2
  DrugBank ID: DB00567
  TTD ID: D0Z5EM
  VARIDT ID: DR00330
  INTEDE ID: DR0284
  ACDINA ID: D00114

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[11]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[12]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[13]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[14]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[15]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[16]
N-acylhomoserine lactone acylase (lacA)	DEIU0XN	A0A0A1VBK6_9BURK	Substrate	[17]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Cephalexin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mycophenolic acid	DMU65NK	Moderate	Altered absorption of Cephalexin due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[63]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of nephrotoxicity by the combination of Cephalexin and Ethacrynic acid.	Essential hypertension [BA00]	[64]
Furosemide	DMMQ8ZG	Moderate	Increased risk of nephrotoxicity by the combination of Cephalexin and Furosemide.	Heart failure [BD10-BD1Z]	[64]
Bumetanide	DMRV7H0	Moderate	Increased risk of nephrotoxicity by the combination of Cephalexin and Bumetanide.	Heart failure [BD10-BD1Z]	[64]
Probenecid	DMMFWOJ	Moderate	Decreased elimination of Cephalexin caused by Probenecid mediated competitive inhibition of renal tubular secretion.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[65]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Cephalexin due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[63]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Hydrazine yellow	E00409	164825	Colorant
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Quinoline yellow WS	E00309	24671	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Carboxymethylcellulose sodium	E00621	Not Available	Adsorbent; Binding agent; Disintegrant; Emulsifying agent; Suspending agent; Viscosity-controlling agent
Carmellose sodium	E00625	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Potassium hydroxide	E00233	14797	Alkalizing agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Cephalexin 250 mg capsule	250 mg	Oral Capsule	Oral
Cephalexin 333 mg capsule	333 mg	Oral Capsule	Oral
Cephalexin 750 mg capsule	750 mg	Oral Capsule	Oral
Cephalexin 500 mg capsule	500 mg	Oral Capsule	Oral
Cephalexin 250 mg tablet	250 mg	Oral Tablet	Oral
Cephalexin 500 mg tablet	500 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4832).
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 061969.
• [3] MedSafe NZ: Levetiracetam
• [4] BDDCS applied to over 900 drugs
• [5] Cephalexin: human studies of absorption and excretion of a new cephalosporin antibiotic. Br J Pharmacol. 1969 Nov;37(3):738-47. doi: 10.1111/j.1476-5381.1969.tb08513.x.
• [6] Thornhill TS, Levison ME, Johnson WD, Kaye D: In vitro antimicrobial activity and human pharmacology of cephalexin, a new orally absorbed cephalosporin C antibiotic. Appl Microbiol. 1969 Mar;17(3):457-61.
• [7] Patel SS, Spencer CM: Latanoprost. A review of its pharmacological properties, clinical efficacy and tolerability in the management of primary open-angle glaucoma and ocular hypertension. Drugs Aging. 1996 Nov;9(5):363-78. doi: 10.2165/00002512-199609050-00007.
• [8] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [9] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [10] Pfeffer M, Jackson A, Ximenes J, de Menezes JP: Comparative human oral clinical pharmacology of cefadroxil, cephalexin, and cephradine. Antimicrob Agents Chemother. 1977 Feb;11(2):331-8. doi: 10.1128/aac.11.2.331.
• [11] Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics. J Med Microbiol. 2004 Mar;53(Pt 3):213-21.
• [12] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [13] Direct evidence for efficient transport and minimal metabolism of L-cephalexin by oligopeptide transporter 1 in budded baculovirus fraction. Biol Pharm Bull. 2009 Aug;32(8):1459-61.
• [14] Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
• [15] Transport and metabolic characterization of Caco-2 cells expressing CYP3A4 and CYP3A4 plus oxidoreductase. Pharm Res. 1999 Sep;16(9):1352-9.
• [16] Population pharmacokinetic analysis of mirtazapine. Eur J Clin Pharmacol. 2004 Sep;60(7):473-80.
• [17] A novel quorum-quenching N-acylhomoserine lactone acylase from Acidovorax sp. strain MR-S7 mediates antibiotic resistance. Appl Environ Microbiol. 2017 Jun 16;83(13). pii: e00080-17.
• [18] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [19] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [20] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [21] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [22] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [23] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [24] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [25] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [26] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [27] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [28] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [29] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [30] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [31] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [32] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [33] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [34] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [35] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
• [36] Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
• [37] Molecular mechanism of renal tubular secretion of the antimalarial drug chloroquine. Antimicrob Agents Chemother. 2011 Jul;55(7):3091-8.
• [38] Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
• [39] FDA Drug Development and Drug Interactions
• [40] Expression of Organic Anion Transporter 1 or 3 in Human Kidney Proximal Tubule Cells Reduces Cisplatin Sensitivity. Drug Metab Dispos. 2018 May;46(5):592-599.
• [41] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [42] Peptide transporter substrate identification during permeability screening in drug discovery: comparison of transfected MDCK-hPepT1 cells to Caco-2 cells. Arch Pharm Res. 2007 Apr;30(4):507-18.
• [43] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [44] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [45] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [46] Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
• [47] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [48] Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes. Alcohol Clin Exp Res. 2008 May;32(5):777-84.
• [49] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [50] Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants. Drug Metab Dispos. 2017 Feb;45(2):130-136.
• [51] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
• [52] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
• [53] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
• [54] Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci. Antimicrob Agents Chemother. 2002 May;46(5):1273-80.
• [55] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [56] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [57] Activities of antibiotics against methicillin-resistant Staphylococcus aureus with particular reference to synergetic effect between ticarcillin and fosfomycin on penicillinase non-producing methicillin-resistant S. aureus. Jpn J Antibiot. 1993 Jun;46(6):421-7.
• [58] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [59] Penicillin-binding protein sensitive to cephalexin in sporulation of Bacillus cereus. Microbiol Res. 1997 Sep;152(3):227-32.
• [60] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [61] Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J Antimicrob Chemother. 1990 Apr;25(4):513-23.
• [62] In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enter... J Infect Dis. 2004 Dec 15;190(12):2162-6.
• [63] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [64] Chrysos G, Gargalianos P, Lelekis M, Stefanou J, Kosmidis J "Pharmacokinetic interactions of ceftazidime and frusemide." J Chemother 7 Suppl (1995): 107-10. [PMID: 8904125]
• [65] Brown G, Zemcov SJ, Clarke AM "Effect of probenecid on cefazolin serum concentrations." J Antimicrob Chemother 31 (1993): 1009-11. [PMID: 8360120]