Ceftriaxone (Page 5 of 7)
Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (I.V.) infusion of a 0.5, 1 or 2 g dose in healthy subjects are presented in Table 3. Multiple intravenous doses ranging from 0.5 to 2 g at 12- to 24-hour intervals resulted in 15% to 36% accumulation of ceftriaxone above single dose values.
TABLE 3: Ceftriaxone Plasma Concentrations After Single Dose Administration
|Dose/Route||Average Plasma Concentrations (mcg/mL)|
|0.5 hr||1 hr||2 hr||4 hr||6 hr||8 hr||12 hr||16 hr||24 hr|
|0.5 gram I.V.*||82||59||48||37||29||23||15||10||5|
|1 gram I.V.*||151||111||88||67||53||43||28||18||9|
|2 grams I.V.*||257||192||154||117||89||74||46||31||15|
Over a 0.15 to 3 g dose range in healthy adult subjects, the mean elimination half-life ranged from 5.8 to 8.7 hours, plasma clearance ranged from 0.58 to 1.45 L/hour, and renal clearance ranged from 0.32 to 0.73 L/hour.
Ceftriaxone is reversibly bound to human plasma proteins and the binding of ceftriaxone decreases with increasing concentration from a value of 95% at plasma concentrations less than 25 mcg/mL to 85% at plasma concentration of 300 mcg/mL. Over a 0.15 to 3 g dose range in healthy adult subjects, the apparent volume of distribution ranged from 5.8 to 13.5 L.
Ceftriaxone crosses the blood placenta barrier.
Ceftriaxone penetrates the inflamed meninges of infants and pediatric patients. The average values of maximum plasma concentration, cerebrospinal fluid (CSF) concentrations, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg intravenous dose and after a 75 mg/kg intravenous dose in pediatric patients suffering from bacterial meningitis are shown in Table 4.
TABLE 4: Average Pharmacokinetic Parameters of Ceftriaxone in Pediatric Patients with Meningitis
|50 mg/kg I.V.||75 mg/kg I.V.|
|Maximum Plasma Concentrations (mcg/mL)||216||275|
|Elimination Half-life (hr)||4.6||4.3|
|Plasma Clearance (mL/hr/kg)||49||60|
|Volume of Distribution (mL/kg)||338||373|
|CSF Concentration – inflamed meninges (mcg/mL)||5.6||6.4|
|Time after dose (hr)||3.7 (±1.6)||3.3 (±1.4)|
After a 1 gram intravenous dose, average concentrations of ceftriaxone, determined from 1 to 3 hours after dosing, were 581 mcg/mL in the gallbladder bile, 788 mcg/mL in the common duct bile, 898 mcg/mL in the cystic duct bile, 78.2 mcg/gram in the gallbladder wall compared to a corresponding concentration of 62.1 mcg/mL in plasma.
Ceftriaxone concentrations in urine are shown in Table 5.
TABLE 5: Urinary Concentrations of Ceftriaxone After Single Dose Administration
|Average Urinary Concentrations (mcg/mL)|
|Dose/Route||0-2 hr||2-4 hr||4-8 hr||8-12 hr||12-24 hr||24-48 hr|
|0.5 gram I.V.||526||366||142||87||70||15|
|1 gram I.V.||995||855||293||147||132||32|
|2 grams I.V.||2692||1976||757||274||198||40|
Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug, and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds.
The elimination of ceftriaxone is not altered by probenecid.
Average pharmacokinetic parameters of ceftriaxone in healthy subjects, elderly subjects, subjects with renal impairment, and subjects with liver disease are summarized in Table 6. Compared to healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with renal or hepatic impairment; therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2 grams per day. Ceftriaxone was not removed to any significant extent from the plasma by hemodialysis. In 6 of 26 dialysis patients, the elimination rate of ceftriaxone was markedly reduced, suggesting that plasma concentrations of ceftriaxone should be monitored in these patients to determine if dosage adjustments are necessary [see Dosage and Administration (2.1) and Warnings and Precautions (5.7)].
TABLE 6: Average Pharmacokinetic Parameters of Ceftriaxone in Humans
|Subject Group||Elimination Half-Life (hr)||Plasma Clearance (L/hr)||Volume of Distribution (L)|
|Healthy Subjects *||5.8-8.7||0.58-1.45||5.8-13.5|
|Elderly Subjects (mean age, 70.5 yr)||8.9||0.83||10.7|
|Patients with Renal Impairment|
|Hemodialysis Patients (0-5 mL/min)†||14.7||0.65||13.7|
|Severe (5-15 mL/min)||15.7||0.56||12.5|
|Moderate (16-30 mL/min)||11.4||0.72||11.8|
|Mild (31-60 mL/min)||12.4||0.70||13.3|
|Patients with Liver Disease||8.8||1.1||13.6|
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