Cefdinir appears to exert little effect on normal human fecal flora. In a study involving seven pediatric patients (0.5 to 12.5 years old) treated with doses ranging from 9 to 11 mg/kg/day for 4 to 14 days, only modest effects on fecal flora were observed. Aerobic and anaerobic counts, except those of enterococci, varied little over time and in no case did glucose nonfermenters or fungi become predominant species for any length of time. 53
Interpretive criteria and quality control parameters have been published for broth microdilution and disk diffusion methods for cefdinir susceptibility testing of pneumococci, Neisseria gonorrhoeae, H. influenzae, E. coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. 17, 39, 54–60 The MIC breakpoint is 1 mg/l (sensitive, ≤1 mg/l; intermediate, 2 mg/l; resistant, ≥4 mg/l) and the zone size breakpoint for disk diffusion testing with a 5-mg disk is 20 mm (resistant, ≤16 mm; intermediate, 17 to 19 mm; sensitive, ≥20 mm) for organisms other than streptococci. 53, 61 MIC and disk diffusion breakpoints have been established for S. pneumoniae and streptococci other than S. pneumoniae. 53
Pharmacokinetic parameters for cefdinir in adults and children are illustrated in Table 2. Absorption appears to be reasonably rapid in children, with a time to peak plasma concentration (T max) of ∼2 h.
Bioavailability of the capsule formulation ranges from 16 to 21%; bioavailability of the suspension formulation is 20% greater than that of the capsule formulation. 53 Food exerts no clinically significant effect on cefdinir bioavailability. 53
Few published data are available regarding tissue and body fluid penetration of cefdinir. In studies utilizing healthy adult volunteers, significant penetration was noted into suction-induced blister fluid (84 to 108%), bronchial mucosal tissue (31 to 41%), bronchial epithelial lining fluid (12 to 15%), tonsillar tissue (24%) and maxillary/ethmoid sinus mucosal tissue (16%). 53, 62, 63 In pediatric patients with acute bacterial otitis media, the mean middle ear fluid concentration 3 h after single 7- and 14-mg/kg doses of cefdinir was 15% that of the corresponding plasma concentration. 53
In adults cefdinir is primarily eliminated as unchanged drug via the renal route. 53, 62 This may not, however, be the case in children based on the low fractional elimination of unchanged drug in children (mean range, 2.7 to 12.7%) compared with that in adults (mean range, 12.7 to 23%). 53, 62 Terminal disposition half-life (t 1/2) is ∼1.5 h in healthy adult and pediatric volunteers. 53, 62 Apparent total body clearance appears to be higher in younger (0- to 3-year-old) than in older (3- to 12-year-old) children, consistent with data obtained with other beta-lactam antimicrobials. 53 In adults with normal renal function, drug accumulation does not occur with multiple once or twice daily administration, and pharmacokinetic parameters are similar for multiple dose as compared with single dose administration. 53
Studies have been conducted in adults evaluating the effect of renal dysfunction and dialysis on cefdinir pharmacokinetics. 53 Decreases in apparent total body clearance and renal clearance of cefdinir were approximately proportional to the reduction in creatinine clearance (CrCl). For example in subjects with CrCl between 30 and 60 ml/min, peak plasma concentration (C max), t 1/2 and area under the plasma concentration-vs.-time curve (AUC) increased ∼2-, 2- and 3-fold, respectively, compared with subjects who had normal renal function. Corresponding increases in subjects with CrCl <30 ml/min were 2-, 5- and 6-fold, respectively.
Simultaneous administration of magnesium-aluminum hydroxide antacid reduced cefdinir bioavailability by 38% (based on C max data) and 44% (based on AUC data). Separating the dose administrations by 2 h eliminated the interaction. 53
The effect of iron on cefdinir bioavailability is controversial. One study described a significant reduction in bioavailability when 1050 mg of ferrous sulfate were coadministered with or 3 h after cefdinir capsule administration. 65 Another study found that concomitant administration of ferrous sulfate (60 mg elemental iron) and multiple vitamins supplemented with iron (10 mg elemental iron) reduced cefdinir bioavailability by 79 and 38%, respectively (based on C max data) and 80 and 31%, respectively (based on AUC data). In contrast iron-fortified infant formula was not found to significantly affect cefdinir bioavailability from the suspension formulation in healthy infants. 53
Cefdinir is an extended spectrum oral cephalosporin with a broad range of activity against Gram-positive and Gram-negative aerobes. It exhibits superior activity against Gram-positive aerobes such as staphylococci and streptococci compared with drugs such as cefixime, cefpodoxime, cefuroxime and ceftibuten. The pharmacokinetic parameters of cefdinir in children are similar to those obtained in adults using similar milligram per m 2 doses (300 mg in adults = 7 mg/kg in children and 600 mg in adults = 14 mg/kg in children). Pharmacokinetic data have thus validated the use of 7 mg/kg twice daily and 14 mg/kg once daily dosing in the pediatric efficacy studies described in the literature 53, 66–68 and in this supplement.
I thank Kari Bunjer for administrative assistance in the preparation of the manuscript.
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