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Neonatal Intensive Care Drug Manual
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| bet | 61/654 | | Sana | 03.01.2022 | | Hajmi | 1,5 Mb. | | #14803 |
Pharmacokinetics
There are 7 reported pharmacokinetic studies of amoxicillin in neonates (4 in children and 13 in adults). In summary statistics, the post menstrual age range of patients for amoxicillin ranged from 29 weeks to 82 years finding mean drug clearance for amoxicillin 10.9 (range 1.3–22.4) L/hour/70kg, and mean volume of distribution for amoxicillin 28.9 (10.7–53.5) L/70kg. There is a lower clearance and higher volume of distribution for amoxicillin in neonates. [20] The elimination half-life of amoxicillin in children averages 1 to 1.2 hours. [7] There are no reported pharmacokinetic data for clavulanate in neonates. In summary statistics, the post menstrual age range for clavulanate ranged from 2.6 to 71 years finding mean drug clearance 13.9 (8.9–17.9) L/hour/70kg, and mean volume of distribution (all ages) (range) for clavulanate 23.9 (21.0– 30.4) L/70kg. [20] The elimination half-life of clavulanate in children averages 1.0 hours. [7] To achieve sufficient amoxicillin and high clavulanate exposure, the optimal regimen is to administer narrower ratio amoxicillin-clavulanate (typically 4:1) in a three times daily regimen. [8] In adults and children, the oral bioavailability of amoxicillin is about 70 to 90% and maximum serum concentrations occur within 60 to 90 minutes of administration. Clavulanate has variable oral bioavailability of 31 to 99%. [7] However, neonates may have reduced bioavailability of oral amoxicillin. In a crossover study in 14 fasting newborn infants 6-13 days old given IM ampicillin or amoxicillin 50 mg/kg twice daily, the mean peak level was 58% (range 35-96%) for oral compared to parenteral dosing, and area under the time-concentration curve was 75% (range 60-101%). [21] There are no data for oral bioavailability of clavulanate in neonates. To decrease the patient's medication burden by prescribing only twice daily amoxicillin -clavulanate, then a higher ratio (e.g. 7:1) can be employed in order to increase amoxicillin exposure (to improve efficacy) and limit clavulanate exposure (to reduce toxicity). Twice-daily regimens are commonly recommended in the treatment of acute otitis media or community-acquired pneumonia during, childhood. [8], Gram-negative organisms require higher and more sustained levels of both amoxicillin as well as the, clavulanic-acid component for optimal therapy. For clinical syndromes in which Gram-negative, pathogens are causative (e.g. urinary tract infection), a narrower ratio (e.g. 4:1) with more frequent, dosing (three or four rather than two times daily) is needed for efficacy. [8],For Gram-positive pathogens, which appear to have a higher affinity for clavulanate and are also, susceptible to lower amoxicillin concentrations, combinations with a wider ratio (e.g. 7:1) appear to be, sufficient in terms of clavulanate exposure. [8], Extreme ratios of 14:1 or 16:1 should be used with caution until more data are available.[8], Impaired renal function: Extra-renal elimination of clavulanate is much more rapid than that of, amoxicillin. Whereas the elimination half-life of amoxicillin increases 6-fold in patients with severe, renal failure, the corresponding increase for clavulanate is only 2.6-fold. [3], No dosage adjustments are required for patients with impaired hepatic function, but amoxicillin-, clavulanic should be used with caution and hepatic function monitored. [3]
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