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Chapter 11 : β-Lactam Prodrugs

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Abstract:

This chapter discusses about β-Lactam Prodrugs. Esters are the most common prodrugs, while amides have been tried but are chemically unstable. Morita et al. studied the absorption of cefazolin and cephradine in neonatal and 1-, 2-, and 3-week-old rats. There is a linear relationship between intestinal absorption of cefazolin and the intraluminal concentration in 1-week-old rats. This absorption is not modified by carnosine or glycylglycine. Conversely, with cephradine, absorption is a saturable phenomenon in rats of the same age, and absorption is inhibited by carnosine and glycylglycine. The β-lactams may be considered tripeptide analogs. It has been shown in rats that there are different transporters and that the β-aminopenicillins and β-aminocephems are absorbed differently according to the pH gradient. The chemical structure of β-lactams interferes with intestinal absorption. The presence of a hydroxyl group on the phenyl nucleus in the para position of ampicillin (amoxicillin) or cephalexin (cefadroxil) increases intestinal absorption. The surface of the intestine is a lipid barrier. As per “pH-partition” model for the absorption of drugs, the degree of absorption of bases and weak acids depends on their liposolubility and their degree of ionization. This hypothesis predicts that molecules with a pK of less than 3 will be weakly absorbed. Penicillins and cephalosporins are antibiotics in which the pK of the carboxyl group is between 2 and 3.

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Tables

Generic image for table
Table 2

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 3

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 4

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 5

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 7

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 8

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 9

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 10

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 11

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 12

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 13

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 15

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
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Table 16

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 17

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 18

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 19

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 20

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 22

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 23

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 24

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 25

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 26

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 27

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 28

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 29

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 30

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 31

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 32

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 33

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 34

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 35

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 36

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11
Generic image for table
Table 37

Citation: Bryskier A. 2005. β-Lactam Prodrugs, p 348-376. In Bryskier, M.D. A (ed), Antimicrobial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555815929.ch11

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