Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (IV) infusion of a 0.5, 1 or 2 g dose and intramuscular (IM) administration of a single 0.5 (250 mg/mL or 350 mg/mL concentrations) or 1 g dose in healthy subjects are presented in Table 1.
Table 1 Ceftriaxone Plasma Concentrations After Single Dose Administration
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ND = Not determined.
*IV doses were infused at a constant rate over 30 minutes.
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 g IV* 82 59 48 37 29 23 15 10 5 0.5 g IM 250 mg/mL 22 33 38 35 30 26 16 ND 5 0.5 g IM 350 mg/mL 20 32 38 34 31 24 16 ND 5 1 g IV* 151 111 88 67 53 43 28 18 9 1 g IM 40 68 76 68 56 44 29 ND ND 2 g IV* 257 192 154 117 89 74 46 31 15
Ceftriaxone was completely absorbed following IM administration with mean maximum plasma concentrations occurring between 2 and 3 hours post-dose. Multiple IV or IM 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.
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Ceftriaxone concentrations in urine are shown in Table 2.
Table 2 Urinary Concentrations of Ceftriaxone After Single Dose Administration
ND = Not determined.
Average Urinary Concentrations (mcg/mL) Dose/Route 0 to 2 hr 2 to 4 hr 4 to 8 hr 8 to 12 hr 12 to 24 hr 24 to 48 hr 0.5 g IV 526 366 142 87 70 15 0.5 g IM 115 425 308 127 96 28 1 g IV 995 855 293 147 132 32 1 g IM 504 628 418 237 ND ND 2 g IV 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. After a 1 g IV 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/g in the gallbladder wall and 62.1 mcg/mL in the concurrent plasma.
Over a 0.15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of <25 mcg/mL to a value of 85% bound at 300 mcg/mL. Ceftriaxone crosses the blood placenta barrier.
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The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg IV dose and after a 75 mg/kg IV dose in pediatric patients suffering from bacterial meningitis are shown in Table 3. Ceftriaxone penetrated the inflamed meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a 75 mg/kg IV dose are also shown in Table 3.
Table 3 Average Pharmacokinetic Parameters of Ceftriaxone in Pediatric Patients with Meningitis 50 mg/kg IV 75 mg/kg IV 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 Range (mcg/mL) 1.3 to 18.5 1.3 to 44 Time after dose (hr) 3.7 (± 1.6) 3.3 (± 1.4)
Compared to that in healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction (Table 4); therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2 g per day. Ceftriaxone was not removed to any significant extent from the plasma by hemodialysis; in six of 26 dialysis patients, the elimination rate of ceftriaxone was markedly reduced.
Table 4 Average Pharmacokinetic Parameters of Ceftriaxone in Humans
*Creatinine clearance
Subject Group Elimination Half-Life (hr) Plasma Clearance (L/hr) Volume of Distribution (L) Healthy Subjects 5.8 to 8.7 0.58 to 1.45 5.8 to 13.5 Elderly Subjects (mean age, 70.5 yr) 8.9 0.83 10.7 Patients with Renal Impairment Hemodialysis Patients (0 to5 mL/min)* 14.7 0.65 13.7 Severe (5 to15 mL/min) 15.7 0.56 12.5 Moderate (16 to 30 mL/min) 11.4 0.72 11.8 Mild (31to 60 mL/min) 12.4 0.70 13.3 Patients with Liver Disease 8.8 1.1 13.6
The elimination of ceftriaxone is not altered when ceftriaxone for injection is co-administered with probenecid.
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