Gentamicin Absorption during Prophylactic Use for Necrotizing Enterocolitis

Miranda, Joaquin C.; Schimmel, Michael S.; Mimms, Gaines M.; Spinelli, Walter; Driscoll, John M.; James, Liao; Rosen, Tove S.

doi:10.1159/000457179

Cited by 11 publications

(8 citation statements)

References 4 publications

(5 reference statements)

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“…Because of the highly polar, cationic nature of aminoglycosides, they are not appreciably absorbed from the gastrointestinal tract unless there is significant disruption of the intestinal mucosa from necrotizing enteritis (Gemer et al, 1983;Miranda et al, 1984). They are not inactivated in the intestine, and are quantitatively eliminated in the feces after oral administration to normal animals.…”

Section: Absorptionmentioning

confidence: 99%

Comparative pharmacokinetics of aminoglycoside antibiotics

Brown

Riviere

1991

Vet Pharm & Therapeutics

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Section: Absorptionmentioning

confidence: 99%

Comparative pharmacokinetics of aminoglycoside antibiotics

Brown

Riviere

1991

Vet Pharm & Therapeutics

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“…SlUdies that have examined ami nog.iycoside CL and postconceptional age have demonstrated strong correlations over a wide range of gestational and postnatal age (Kasik et al 1985;Kildoo et al 1984;Landers et al 1984;Miranda et al 1985;Thomson et al 1988). SlUdies that have examined ami nog.iycoside CL and postconceptional age have demonstrated strong correlations over a wide range of gestational and postnatal age (Kasik et al 1985;Kildoo et al 1984;Landers et al 1984;Miranda et al 1985;Thomson et al 1988).…”

Section: Eliminationmentioning

confidence: 99%

Clinical Pharmacokinetics of Antibacterial Drugs in Neonates

Paap

Nahata

1990

Clinical Pharmacokinetics

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Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy. The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the beta-lactams. Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t1/2) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients. Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates. Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome. There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety.

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“…This may due to the high polarity and cationic nature of the drug, which result in scant absorption from gastrointestinal tract. However, oral bioavailability may increase slightly (2%) if significant disruption of the gastrointestinal mucosa occurs owing to necrotizing enteritis (Gemer et al, 1983;Miranda et al, 1984). Nevertheless, gentamicin is still used to treat enteritis associated with some susceptible aerobic Gram-negative bacteria.…”

Section: Discussionmentioning

confidence: 99%

Comparative Pharmacokinetics of Gentamicin after Intravenous, Intramuscular, Subcutaneous and Oral Administration in Broiler Chickens

2007

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The pharmacokinetics and bioavailability of gentamicin sulphate (5 mg/kg body weight) were studied in 50 female broiler chickens after single intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.) and oral administration. Blood samples were collected at time 0 (pretreatment), and at 5, 15 and 30 min and 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Gentamicin concentrations were determined using a microbiological assay and Bacillus subtillis ATCC 6633 as a test organism. The limit of quantification was 0.2 microg/ml. The plasma concentration-time curves were analysed using non-compartmental methods based on statistical moment theory. Following i.v. administration, the elimination half-life (t (1/2beta)), the mean residence time (MRT), the volume of distribution at steady state (V (ss)), the volume of distribution (V (d,area)) and the total body clearance (Cl(B)) were 2.93 +/- 0.15 h, 2.08 +/- 0.12 h, 0.77 +/- 0.05 L/kg, 1.68 +/- 0.39 L/kg and 5.06 +/- 0.21 ml/min per kg, respectively. After i.m. and s.c. dosing, the mean peak plasma concentrations (C (max)) were 11.37 +/- 0.73 and 16.65 +/- 1.36 microg/ml, achieved at a post-injection times (t (max)) of 0.55 +/- 0.05 and 0.75 +/- 0.08 h, respectively. The t (1/2beta) was 2.87 +/- 0.44 and 3.48 +/- 0.37 h, respectively after i.m. and s.c. administration. The V (d,area) and Cl(B) were 1.49 +/- 0.21 L/kg and 6.18 +/- 0.31 ml/min per kg, respectively, after i.m. administration and were 1.43 +/- 0.19 L/kg and 4.7 +/- 0.33 ml/min per kg, respectively, after s.c. administration. The absolute bioavailability (F) of gentamicin after i.m. administration was lower (79%) than that after s.c. administration (100%). Substantial differences in the resultant kinetics data were obtained between i.m. and s.c. administration. The in vitro protein binding of gentamicin in chicken plasma was 6.46%.

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Gentamicin Absorption during Prophylactic Use for Necrotizing Enterocolitis

Cited by 11 publications

References 4 publications

Comparative pharmacokinetics of aminoglycoside antibiotics

Comparative pharmacokinetics of aminoglycoside antibiotics

Clinical Pharmacokinetics of Antibacterial Drugs in Neonates

Comparative Pharmacokinetics of Gentamicin after Intravenous, Intramuscular, Subcutaneous and Oral Administration in Broiler Chickens

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