Aztreonam in human serum and breast milk.

Fleiss, PM; Richwald, G. A.; Gordon, J; Stern, Mariana C.; Frantz, M; Devlin, RG

doi:10.1111/j.1365-2125.1985.tb02677.x

Cited by 27 publications

(8 citation statements)

References 5 publications

(4 reference statements)

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“…This is in agreement with poor lipid solubility, as was mentioned earlier with respect to the CSF. The same applies for the very low concentrations reported in the milk of lactating women (Fleiss et al 1985 …”

Section: Other Compartmentssupporting

confidence: 57%

Clinical Pharmacokinetics of Aztreonam

Mattie

1988

Clinical Pharmacokinetics

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Aztreonam (azthreonam) is practically completely absorbed after intramuscular injection. After intravenous injection plasma concentrations follow a 2-compartment open model, with a t1/2 alpha of 0.20 hours. Volume of distribution at steady-state (Vdss) after intravenous or intramuscular injection is about 0.16 L/kg (0.42 L/kg for the free drug). After oral administration less than 1% of the drug is absorbed. Over a large dosage range plasma concentrations increase linearly with dose. No accumulation occurs after multiple dosing. Plasma binding in healthy subjects is about 56% and is not concentration dependent. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma concentration seems to depend mainly on the composition of the tissue. In inflamed meninges, penetration of aztreonam into CSF is more rapid than with uninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breast milk. The main route of elimination of aztreonam is by the kidney, partly by active tubular excretion, but this can be inhibited by probenecid. Extrarenal clearance is probably due to excretion by the liver. Metabolism occurs to a very limited extent. Total plasma clearance in healthy adults is about 140 ml/min (8.4 L/h) or 2 ml/min/kg (0.12 L/h/kg), and terminal half-life is 1.7 hours. In children clearance is similar to that in adults when expressed as a function of bodyweight, but in neonates, especially in low birthweight infants, it is less [about 1 ml/min/kg (0.06 L/h/kg)]. In various disease states the Vdss of aztreonam is not appreciably different from that found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Other Compartmentssupporting

confidence: 57%

Clinical Pharmacokinetics of Aztreonam

Mattie

1988

Clinical Pharmacokinetics

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“…aztreonam, captopril, diltiazem and (Fehrenbach, 1987). tinidazole (Devlin & Fleiss, 1981;Evaldson et Maternal antimicrobials are often required in Fleiss et al, 1985;Okada et al, 1985). the postnatal period and a prescribing survey in These studies have concentrated on drug kinetics Northern Ireland showed that 4% of puerperal and while this is a very important aspect, previous mothers received metronidazole therapy (Passstudies have given little information about infant more et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Metronidazole excretion in human milk and its effect on the suckling neonate.

Passmore

McElnay

Rainey

et al. 1988

Brit J Clinical Pharma

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1. Milk and plasma metronidazole and hydroxymetronidazole concentrations were measured in 12 breast‐feeding patients following multiple doses of metronidazole (400 mg three times daily). All patients received metronidazole in combination with other broad spectrum antibiotics. 2. Plasma concentrations of both parent drug and metabolite were measured in seven suckling infants. Thirty‐five infants were monitored for adverse reactions to maternal metronidazole therapy and two further groups of suckling infants, those whose mothers received either ampicillin alone or no drug therapy, were recruited as controls. 3. The mean milk to plasma ratio (M/P) was 0.9 for metronidazole and 0.76 for hydroxymetronidazole while the mean milk metronidazole concentrations (around Cmax) were 15.5 micrograms ml‐1. The mean milk hydroxymetronidazole concentration was 5.7 micrograms ml‐ 1. 4. Infant plasma metronidazole concentrations ranged from 1.27 micrograms ml‐1 to 2.41 micrograms ml‐1, and the corresponding hydroxymetronidazole concentrations from 1.1 to 2.4 micrograms ml‐1. 5. There were no significant increases in adverse effects in infants which could be attributable to maternal metronidazole therapy. 6. Metronidazole was excreted in milk at concentrations which caused no serious reactions in the infants studied. The drug may therefore be administered at doses of 400 mg three times daily to mothers wishing to breast‐feed their infants.

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“…When equal doses of aztreonam were administered by two separate routes, intramuscular and intravenous, to two groups of women the resultant M/P ratios were indistinguishable [7], The ratios obtained after oral or intra muscular administration of butorphanol [8] were clearly different, but this was confounded by the increase in dose for the oral route.…”

Section: Discussionmentioning

confidence: 99%

“…The ratio appears to fall after administration of procainamide [23] and to rise after dosing with baclofen [24], cimetidine [21], hydro chlorothiazide [25] and aztreonam [7], The temporal variance of the M/P ratio for aztreonam was found for two parenteral routes of administration. The pattern of variance can be biphasic, increasing with time then declin ing after 12-16 h for captopril [26], digoxin [27] and phenytoin [11], Pat terns of variation in the M/P ratio for other drugs have been summarized recently [1].…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic Factors Contributing to Variance in the Milk to Plasma Ratio for Acetaminophen in the Goat

Wilson¹,

Hinson²,

Johnson³

et al. 1987

Dev Pharmacol Ther

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A single-point estimate of the milk to plasma (M/P) drug ratio presupposes an invariant ratio. This may lead to erroneous conclusions about the amount of drug excreted in breast milk. A variance of the M/P ratio with regard to time has been shown for acetaminophen under standardized biologic conditions in the lactating goat. This ratio is potentially confounded by such factors as route of administration, dose amount and duration of exposure to the drug. Each factor was evaluated by computer simulations of the M/P ratio and by derivation of a ratio from empirical data in the goat. Route of administration was found to influence both the pattern and magnitude of the M/P ratio after acetaminophen dosing in the goat. Similar, but less, effects were found for duration of dosing. Dose itself did not influence the ratio. A temporal basis exists for each confounding factor. We thus propose that the M/P ratio is fundamentally variant with time under a standard set of biologic conditions. The contributing variance of confounding factors must be assessed if drug in milk dosing of the infant is to be accurately evaluated by use of the M/P ratio.

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Aztreonam in human serum and breast milk.

Cited by 27 publications

References 5 publications

Clinical Pharmacokinetics of Aztreonam

Clinical Pharmacokinetics of Aztreonam

Metronidazole excretion in human milk and its effect on the suckling neonate.

Pharmacologic Factors Contributing to Variance in the Milk to Plasma Ratio for Acetaminophen in the Goat

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