Is Keflex (Cephalexin) a Highly Bioavailable Oral Antibiotic?
Yes, cephalexin is a highly bioavailable oral antibiotic with near-complete absorption from the gastrointestinal tract.
Pharmacokinetic Evidence of High Bioavailability
Cephalexin achieves 90–100% urinary recovery of the administered dose within 6–8 hours, indicating near-complete oral absorption. 1
The drug is totally and rapidly absorbed in the upper intestine, not from the stomach, which contributes to its high bioavailability and minimal gastrointestinal disturbance. 1
Peak serum concentrations are achieved predictably 2 hours after oral administration, with mean levels of 12.0 ± 0.8 mcg/mL following a single 500 mg dose in healthy adults. 2
A 250 mg oral dose produces mean peak serum concentrations of 7.7 mcg/mL, while a 500 mg dose achieves 12.3 mcg/mL, demonstrating dose-proportional pharmacokinetics consistent with reliable absorption. 3
Food does not interfere with cephalexin absorption, further supporting its robust oral bioavailability in clinical practice. 3
Clinical Implications of High Bioavailability
The high and predictable absorption allows cephalexin to be administered in relatively high oral doses (up to 4 grams daily in divided doses) without gastrointestinal irritation. 1
Because cephalexin is absorbed high in the intestinal tract, it does not disturb lower bowel flora, reducing the risk of antibiotic-associated diarrhea compared to agents absorbed more distally. 1
Urinary concentrations of 500–1,000 mcg/mL follow 250–500 mg oral doses, levels many times greater than the minimum inhibitory concentration for common urinary pathogens, making oral therapy highly effective for UTIs. 1
The mean peak serum concentration after a 500 mg oral dose (12.3 mcg/mL) is adequate to inhibit all group A streptococci, Streptococcus pneumoniae, and Staphylococcus aureus, as well as 85% of E. coli strains. 3
Factors Affecting Bioavailability
Probenecid enhances both peak serum concentration and duration of antibiotic activity by blocking renal tubular secretion, though this is rarely used clinically. 3
In children, higher doses per kilogram may be needed compared to adults due to greater body water turnover, but absorption remains complete and predictable. 1
Renal impairment significantly prolongs serum half-life (from 1.03 hours in normal subjects to 8.47 hours in anuric patients) but does not reduce absorption; dose adjustment is based on creatinine clearance, not bioavailability concerns. 2
Comparison to Other Oral Cephalosporins
A systematic review of cephalexin pharmacokinetics confirms dose-proportional increases in AUC₀₋∞ and Cmax across multiple studies, validating its consistent high bioavailability. 4
In patients with renal impairment, cephalexin's Cmax was recorded to be 0.5-fold higher than cefaclor, suggesting superior or equivalent absorption characteristics. 4
Common Pitfalls
Do not assume that high bioavailability means cephalexin penetrates all tissues equally; it does not enter host tissue cells, spinal fluid, or aqueous humor, which accounts for its low side-effect profile but limits use in CNS or intracellular infections. 1
Despite excellent oral absorption, cephalexin has a short serum half-life (approximately 1 hour in normal renal function), necessitating dosing every 6 hours (four times daily) to maintain therapeutic concentrations for serious infections. 2, 5
Twice-daily or thrice-daily dosing regimens are sometimes prescribed to improve adherence, but these require higher per-dose amounts (22–45 mg/kg BID or 15–25 mg/kg TID for pediatric MSSA infections with MIC 1–2 mg/L) to compensate for the short half-life. 5