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2D Structure
Also known as: 61-72-3, Cloxacillinum, Cloxacilina, Cloxacilline, Syntarpen, Methocillin s
Molecular Formula
C19H18ClN3O5S
Molecular Weight
435.9  g/mol
InChI Key
LQOLIRLGBULYKD-JKIFEVAISA-N
FDA UNII
O6X5QGC2VB

A semi-synthetic antibiotic that is a chlorinated derivative of OXACILLIN.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(2S,5R,6R)-6-[[3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
2.1.2 InChI
InChI=1S/C19H18ClN3O5S/c1-8-11(12(22-28-8)9-6-4-5-7-10(9)20)15(24)21-13-16(25)23-14(18(26)27)19(2,3)29-17(13)23/h4-7,13-14,17H,1-3H3,(H,21,24)(H,26,27)/t13-,14+,17-/m1/s1
2.1.3 InChI Key
LQOLIRLGBULYKD-JKIFEVAISA-N
2.1.4 Canonical SMILES
CC1=C(C(=NO1)C2=CC=CC=C2Cl)C(=O)NC3C4N(C3=O)C(C(S4)(C)C)C(=O)O
2.1.5 Isomeric SMILES
CC1=C(C(=NO1)C2=CC=CC=C2Cl)C(=O)N[C@H]3[C@@H]4N(C3=O)[C@H](C(S4)(C)C)C(=O)O
2.2 Other Identifiers
2.2.1 UNII
O6X5QGC2VB
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Chloroxacillin

2. Cloxacillin Sodium

3. Cloxacillin, Sodium

4. Sodium Cloxacillin

5. Sodium, Cloxacillin

6. Syntarpen

7. Tegopen

2.3.2 Depositor-Supplied Synonyms

1. 61-72-3

2. Cloxacillinum

3. Cloxacilina

4. Cloxacilline

5. Syntarpen

6. Methocillin S

7. Cloxacillin Sodium

8. Tegopen

9. Clossacillina [dcit]

10. (3-(o-chlorophenyl)-5-methyl-4-isoxazolyl)penicillin

11. Cloxacillin (inn)

12. Chebi:49566

13. 6-(3-(o-chlorophenyl)-5-methyl-4-isoxazolecarboxamido)penicillanic Acid

14. O6x5qgc2vb

15. (2s,5r,6r)-6-[[3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid

16. Chembl891

17. 6-(((3-(2-chlorophenyl)-5-methyl-4-isoxazolyl)carbonyl)amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic Acid

18. Chloroxacillin

19. Clossacillina

20. (2s,5r,6r)-6-({[3-(2-chlorophenyl)-5-methylisoxazol-4-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid

21. Cloxacillin [inn]

22. Cloxacillin [inn:ban]

23. Cloxacilina [inn-spanish]

24. Cloxacilline [inn-french]

25. Cloxacillinum [inn-latin]

26. Brl 1621

27. Methylchlorphenylisoxazoryl-penicillin

28. Tegopen (sodium Monohydrate)

29. 4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid, 6-[[[3-(2-chlorophenyl)-5-methyl-4-isoxazolyl]carbonyl]amino]-3,3-dimethyl-7-oxo-, (2s,5r,6r)-

30. Orbenin (tn)

31. Mcipc

32. Hsdb 3042

33. Einecs 200-514-7

34. Unii-o6x5qgc2vb

35. P-25 (sodium Monohydrate)

36. Cloxacillinna

37. Cloxapen (sodium Monohydrate)

38. Brl-1621 (sodium Monohydrate)

39. (2s,5r,6r)-6-(3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid

40. Cloxacillin ,(s)

41. 4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic Acid, 6-(((3-(2-chlorophenyl)-5-methyl-4-isoxazolyl)carbonyl)amino)-3,3-dimethyl-7-oxo-, (2s-(2alpha,5alpha,6beta))-

42. Spectrum_001345

43. Cloxacillin, Antibiotic For Culture Media Use Only

44. Cloxacillin [mi]

45. Prestwick0_000186

46. Prestwick1_000186

47. Prestwick2_000186

48. Prestwick3_000186

49. Spectrum2_001143

50. Spectrum3_000360

51. Spectrum4_000296

52. Spectrum5_000783

53. Cloxacillin [hsdb]

54. Epitope Id:120363

55. Cloxacillin [vandf]

56. Schembl2953

57. Cloxacillin [mart.]

58. Bspbio_000111

59. Bspbio_002059

60. Cloxacillin [who-dd]

61. Kbiogr_000852

62. Kbioss_001825

63. 4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic Acid, 6-(3-(o-chlorophenyl)-5-methyl-4-isoxazolecarboxamido)-3,3-dimethyl-7-oxo-

64. Divk1c_000736

65. Spbio_001065

66. Spbio_002032

67. Bpbio1_000123

68. Dtxsid5022853

69. Gtpl11126

70. Hy-b0466a

71. Kbio1_000736

72. Kbio2_001825

73. Kbio2_004393

74. Kbio2_006961

75. Kbio3_001279

76. Brl1621

77. Ninds_000736

78. Bcp24144

79. Zinc3875417

80. Bdbm50022788

81. Db01147

82. Idi1_000736

83. (2s,5r,6r)-6-[[3-(2-chlorophenyl)-5-methyl-isoxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid

84. (2s,5r,6r)-6-[3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-amido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid

85. 4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic Acid, 6-(3-(o-chlorophenyl)-s-methyl-4-isoxazolecarboxamido)-3,3-dimethyl-7-oxo-

86. Sbi-0051319.p003

87. Cs-0028411

88. C06923

89. D07733

90. 242c583

91. Q422219

92. W-105105

93. Brd-k01244426-236-05-5

94. Brd-k01244426-236-08-9

95. Oxacillin Sodium Monohydrate Impurity E [ep Impurity]

96. 6-(3-o-chlorophenyl-5-methylisoxazol-4-ylamido) Penicillanic Acid

97. 6-(3-o-chlorophenyl-5-methylisoxazol-4-ylamido)penicillanic Acid

98. (2s,5r,6r)-6-(3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido)-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic Acid

99. (2s,5r,6r)-6-{[3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic Acid

100. 6-{[3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carbonyl]-amino}-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic Acid

2.4 Create Date
2005-06-24
3 Chemical and Physical Properties
Molecular Weight 435.9 g/mol
Molecular Formula C19H18ClN3O5S
XLogP32.4
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count7
Rotatable Bond Count4
Exact Mass435.0655696 g/mol
Monoisotopic Mass435.0655696 g/mol
Topological Polar Surface Area138 Ų
Heavy Atom Count29
Formal Charge0
Complexity722
Isotope Atom Count0
Defined Atom Stereocenter Count3
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Penicillins

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


...ITS USE SHOULD BE LIMITED TO TREATING INFECTIONS CAUSED BY PENICILLINASE-PRODUCING SUSCEPTIBLE MICROORGANISMS WHICH ARE RESISTANT TO PENICILLIN G. ...CAN BE USED IN COMBINATION WITH AMPICILLIN IN TREATMENT OF URINARY TRACT INFECTIONS CAUSED BY GRAM-NEGATIVE BACILLI. /MONOHYDRATE/

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1129


METHICILLIN-RESISTANT STAPHYLOCOCCI ARE ALSO SENSITIVE TO CLOXACILLIN, SO THAT DRUG IS USEFUL IN TREATING INFECTIONS WHICH HAVE BECOME RESISTANT TO METHICILLIN. /MONOHYDRATE/

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1129


IN FEW INSTANCES, IT IS NECESSARY TO INTERDICT FUTURE USE OF PENICILLIN BECAUSE OF RISK OF DEATH, & PT SHOULD BE SO WARNED. IT MUST AGAIN BE STRESSED THAT FATAL EPISODES OF ANAPHYLAXIS HAVE FOLLOWED INGESTION OF VERY SMALL DOSES OF THIS ANTIBIOTIC. /PENICILLINS/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1082


For more Therapeutic Uses (Complete) data for CLOXACILLIN (19 total), please visit the HSDB record page.


4.2 Drug Warning

Penicillins are distributed into breast milk, some in low concentrations. Although significant problems in humans have not been documented, the use of penicillins by nursing mothers may lead to sensitization, diarrhea, candidiasis, and skin rash in the infant. /Penicillins/

USP Convention. USPDI - Drug Information for the Health Care Professional. 15 th ed. Volume 1. Rockville, MD: United States Pharmacopeial Convention, Inc., 1995. (Plus updates.), p. 2151


Many penicillins have been used in pediatric patients and no pediatrics-specific problems have been documented to date. However, the incompletely developed renal function of neonates and young infants may delay the excretion of renally eliminated penicillins. /Penicillins/

USP Convention. USPDI - Drug Information for the Health Care Professional. 15 th ed. Volume 1. Rockville, MD: United States Pharmacopeial Convention, Inc., 1995. (Plus updates.), p. 2151


Penicillins have been used in geriatric patients and no geriatrics-specific problems have been documented to date. However, elderly patients are more likely to have age-related renal function impairment, which may require an adjustment in dosage in patients receiving penicillins. /Penicillins/

USP Convention. USPDI - Drug Information for the Health Care Professional. 15 th ed. Volume 1. Rockville, MD: United States Pharmacopeial Convention, Inc., 1995. (Plus updates.), p. 2151


Prolonged use of penicillins may lead to the development of oral candidiasis. /Penicillins/

USP Convention. USPDI - Drug Information for the Health Care Professional. 15 th ed. Volume 1. Rockville, MD: United States Pharmacopeial Convention, Inc., 1995. (Plus updates.), p. 2151


For more Drug Warnings (Complete) data for CLOXACILLIN (16 total), please visit the HSDB record page.


4.3 Minimum/Potential Fatal Human Dose

...PENICILLIN G LIES ON BORDERLINE BETWEEN TOXICITY CLASSES 2 & 3. 2= SLIGHTLY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 5-15 G/KG, BETWEEN 1 PINT & 1 QUART FOR 70 KG PERSON (150 LB). 3= MODERATELY TOXIC; PROBABLE ORAL LETHAL DOSE (HUMAN) 0.5-5 G/KG, BETWEEN 1 OZ & 1 PINT (OR 1 LB) FOR 70 KG PERSON (150 LB). /PENICILLINS/

Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-171


4.4 Drug Indication

Cloxacillin is indicated for the treatment of beta-hemolytic streptococcal, pneumococcal, and staphylococcal infections (including beta-lactamase producing organisms).


5 Pharmacology and Biochemistry
5.1 Pharmacology

Cloxacillin is a semisynthetic antibiotic in the same class as penicillin. Cloxacillin is for use against staphylococci that produce beta-lactamase.


5.2 MeSH Pharmacological Classification

Anti-Bacterial Agents

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)


5.3 ATC Code

J - Antiinfectives for systemic use

J01 - Antibacterials for systemic use

J01C - Beta-lactam antibacterials, penicillins

J01CF - Beta-lactamase resistant penicillins

J01CF02 - Cloxacillin


5.4 Absorption, Distribution and Excretion

Absorption

Well absorbed from the gastrointestinal tract.


.../ANTIMICROBIAL AGENTS/ ARE RAPIDLY BUT INCOMPLETELY (30-80%) ABSORBED FROM GI TRACT. ABSORPTION OF DRUGS IS MORE EFFICIENT WHEN THEY ARE TAKEN ON AN EMPTY STOMACH. PEAK PLASMA CONCN ARE ATTAINED BY 1 HR & APPROX 5-10 UG/ML AFTER INGESTION OF 1 G OF OXACILLIN, & SIMILAR VALUES ARE OBTAINED WITH CLOXACILLIN.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1077


SINCE ABSORPTION IS LESS THAN COMPLETE, HIGHER PLASMA CONCN ARE ACHIEVED FOLLOWING IM INJECTION, & LARGER QUANTITIES OF DRUGS ARE RECOVERABLE IN URINE. ...BOUND TO PLASMA ALBUMIN TO GREAT EXTENT (APPROX 90-95%); NONE IS REMOVED FROM CIRCULATION TO SIGNIFICANT DEGREE BY HEMODIALYSIS.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1077


NORMALLY, ABOUT ONE HALF OF.../DRUG/ IS EXCRETED IN URINE IN FIRST 6 HR AFTER CONVENTIONAL ORAL DOSE. THERE IS ALSO SIGNIFICANT HEPATIC ELIMINATION...IN BILE.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1077


ISOXAZOLYL PENICILLINS ARE RAPIDLY EXCRETED BY KIDNEY, & CONCURRENT ADMIN OF PROBENECID RESULTS IN HIGHER & MORE PERSISTENT PLASMA CONCN. /PENICILLINS/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1077


For more Absorption, Distribution and Excretion (Complete) data for CLOXACILLIN (16 total), please visit the HSDB record page.


5.5 Metabolism/Metabolites

Cloxacillin, like other penicillins, appears to be metabolized via breakage of the beta-lactam ring to form an inactive penicilloic acid metabolite.


PENICILLIN CAN UNDERGO SLOW CONVERSION IN VIVO TO INTERMEDIATES, SUCH AS PENICILLENIC ACID, WHICH CAN REACT WITH APPROPRIATE CONSTITUENTS OF TISSUES. /PENICILLINS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1147


Cloxacillin is partially metabolized to active and inactive metabolites. In one study following administration of a single 500-mg oral cloxacillin dose, 22% of the absorbed dose was hydrolyzed to penicilloic acids which are microbiologically inactive. Cloxacillin is also hydroxylated to a small extent to a microbiologically active metabolite which appears to be as active as cloxacillin.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 264


5.6 Biological Half-Life

HALF-LIVES...BETWEEN 30 AND 60 MINUTES.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1078


IN CHILDREN BEING TREATED FOR STAPHYLOCOCCAL INFECTIONS, MEAN ELIMINATION HALF-LIFE WAS 71 MIN.

PMID:707507 BURCKART GJ ET AL; AM J HOSP PHARM 35 (11): 1380-2 (1978)


The serum half-life of cloxacillin in adults with normal renal function is 0.4-0.8 hr.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 264


The serum half-life of cloxacillin is slightly prolonged in patients with impaired renal function and has been reported to range from 0.8-2.3 hr in patients with severe renal impairment.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 264


In one study in children 1 week to 2 years of age, the serum elimination half-life of cloxacillin was 0.8-1.5 hr. Serum concentrations of cloxacillin are generally higher and the serum half-life more prolonged in neonates than in older children.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 95. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1995 (Plus Supplements 1995)., p. 264


5.7 Mechanism of Action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, cloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cloxacillin interferes with an autolysin inhibitor.


...ITS ANTIBACTERIAL SPECTRUM AGAINST GRAM-POSITIVE BACTERIA IS LIKE THAT OF PENICILLIN EXCEPT IT IS BROADER BY MARGIN OF THOSE STRAINS OR SPECIES THAT PRODUCE PENICILLINASE. ...IT IS LESS ACTIVE THAN PENICILLIN G AGAINST NON-PENICILLINASE-PRODUCING BACTERIA, ESPECIALLY STREPTOCOCCI. /CLOXACILLIN MONOHYDRATE/

Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1129


SINCE PENICILLIN HAS NO EFFECT ON EXISTING CELL WALLS, BACTERIA MUST BE MULTIPLYING FOR BACTERIAL ACTION OF PENICILLIN TO BE MANIFEST. /PENICILLINS/

Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1135


The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/

Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 953


Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

USP Convention. USPDI - Drug Information for the Health Care Professional. 15 th ed. Volume 1. Rockville, MD: United States Pharmacopeial Convention, Inc., 1995. (Plus updates.), p. 2150


TOLERANCE DEVELOPED TO MULTIPLE DOSING. /PENICILLINS/

Gosselin, R.E., H.C. Hodge, R.P. Smith, and M.N. Gleason. Clinical Toxicology of Commercial Products. 4th ed. Baltimore: Williams and Wilkins, 1976., p. II-171