ドリペネム

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Carbapenems

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Mild, transient, asymptomatic elevations in serum aminotransferase levels occur in 1% to 5% of patients receiving parenteral doripenem for 5 to 14 days. These abnormalities are usually self-limited and asymptomatic and rarely above 5 times the upper limit of normal. In the limited period that it has been available, no cases of hepatitis with jaundice have been reported. Nevertheless, several instances of cholestatic jaundice arising during or shortly after therapy have been reported with other carbapenems. The latency to onset has been within 1 to 3 weeks and the pattern of enzyme elevations is usually cholestatic. Immunoallergic features can occur, but autoantibodies are rare. The course is usually self-limiting, but at least one case of vanishing bile duct syndrome related to a carbapenem has been reported. Doripenem and other carbapenems have not been linked to cases of acute liver failure.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Doripenem

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Doripenem is a broad-spectrum carbapenem antibiotic with activity against many gram-positive and gram-negative aerobic bacteria, as well as a variety of anaerobes. Like other beta-lactam antibiotics, doripenem's bactericidal mechanism of action is mostly due to cell death after inhibition of bacterial enzymes called penicillin-bindng proteins (PBPs), which are responsible for peptidoglycan cross-linking during the synthesis of the bacterial cell wall. Carbapenems mainly have high affinity for PBPs 1a, 1b, 2 and 3. Inhibition of each PBP usually results in a different inactivating mechanism. Inhibition of PBPs 1a and 1b results in fast bacterial killing through the formation of spheroplasts, inhibition of PBP 2 results in rod-shaped bacteria to become spherical, and inhibition of PBP 3 results in filamentous-shaped organisms. The PBPs preferentially bound by different carbapenems depend on the organism. In E.coli and P.aeruginosa, doripenem binds to PBP 2, which is involved in the maintenance of cell shape, as well as to PBPs 3 and 4. Doripenem has a 1-beta-methyl side chain, which allows it to be relatively resistant to dehydropeptidase, as well as a trans-alpha-1-hydroxyethyl group at position 6 which provides beta-lactamase resistance. Like other carbapenems, doripenem is different from most beta-lactams due to its stability against hydrolysis by most beta-lactamases, including penicillinases, cephalosporinases, ESBL, and Amp-C producing enterobacteriaceae.

BHV525JOBH

DORIPENEM

Chemical Structure [CS] - Carbapenems

Established Pharmacologic Class [EPC] - Penem Antibacterial

Doripenem is a Penem Antibacterial.

Doripenem is administered intravenously as an infusion. There was no accumulation of doripenem following mulitiple infusions of either 500mg or 1g administered every 8 hours for 7-10 days in subjects with normal renal function.

Doripenem is primarily eliminated unchanged by the kidneys and undergoes glomerular filtration and active tubular secretion. A mean of 71% and 15% of the dose was recovered in urine as unchanged drug and the ring-opened metabolite, respectively, within 48 hours of 500 mg dose in healthy adults. Following the administration of a single 500 mg dose of radiolabeled doripenem to healthy adults, less than 1% of the total radioactivity was recovered in feces after one week.

The average Vd is 16.8 L (8.09-55.5 L) at steady-state in healthy subjects. Doripenem penetrates into many tissues and fluids, including potential sites of approved indication infections.

10.3 L/hour.