Article Figures & Data
Figures
- Fig. 1.
Changes in the urinary pH over 24 h in healthy subjects treated with ammonium chloride (●), sodium bicarbonate (▵), or water (○). Values represent means ± SDs for nine subjects.
Tables
- Table 1.
Influence of urinary pH on ciprofloxacin pharmacokinetics in plasma: a comparison between pharmacokinetic variables on three separate occasions under different conditions of urinary pH
Pharmacokinetic variablesa Resultb(SD) under treatment with: NaHCO3 NH4Cl H2O C max(μg/ml) 1.729 (0.33) 1.506 (0.238) 1.804 (0.421) T max(h) 1.2 (0.2) 1.3 (0.5) 1.0 (0.4) t 1/2(h) 4.6 (1.6) 4.3 (1.1) 4.2 (0.8) AUC (μg · h/ml) 5.147 (0.680) 5.320 (0.770) 5.649 (0.884) CL/F(liters/h) 37.971 (6.711) 39.011 (5.599) 37.464 (5.194) V/F(liters) 248.762 (78.602) 234.484 (46.28) 223.377 (37.52) CLR(liters/h) 16.08 (3.02) 16.78 (2.67) 16.31 (2.67) Ae (mg) 82.4 (16.5) 88.4 (14.5) 90.53 (9.8) ↵a Tmax, time to peak concentration in plasma; t 1/2, apparent elimination half-life; AUC, area under the plasma concentration-time curve (0 to 24 h); CL/F, apparent total body clearance;V/F, apparent volume of distribution; CLR, renal clearance; Ae, amount of unchanged drug excreted.
↵b The pharmacokinetic parameters were calculated according to a two-compartment open model with first-order absorption. ANOVA was utilized to describe significant differences in the pharmacokinetic parameters and urinary pH; all differences were not significant.
- Table 2.
Amount of unchanged drug excreted into urine at various time periods after treatment with ammonium chloride, sodium bicarbonate, or watera
Collection period (h) Amt (mg) of unchanged drug (SD) under treatment with: NaHCO3 NH4Cl H2O 0–2 22.426 (9.679) 24.756 (8.564) 26.251 (5.156) 2–4 20.099 (6.690) 19.877 (5.327) 21.988 (9.145) 4–6 12.763 (3.253) 12.695 (5.696) 13.700 (3.366) 6–8 8.220 (2.015) 11.098 (5.958) 9.314 (3.884) 8–12 10.935 (2.269) 10.116 (2.546) 10.598 (2.410) 12–24 9.899 (2.604) 8.304 (3.246) 8.608 (3.927) ↵a ANOVA was utilized to describe significant differences; all differences were not significant.
- Table 3.
Influence of pH and Ca2+ and Mg2+cations on the MICs of ciprofloxacin and sparfloxacin
Strain and drug MIC [μg/ml (fold increase)] in brotha at pH: 8.0 (MHB-A) 7.2 5.8 (MHB-A) MHB-A MHB-B MHB-C MHB-D E. coli NIHJ JC-2 Ciprofloxacin 0.016 0.031 (2) 0.031 (2) 0.063 (4) 0.063 (4) 0.125 (8) Sparfloxacin 0.008 0.031 (4) 0.031 (4) 0.063 (8) 0.063 (8) 0.25 (31) P. aeruginosa ATCC 27853 Ciprofloxacin 0.50 0.50 (1) 0.50 (1) 0.50 (1) 1 (2) 2 (4) Sparfloxacin 0.50 2 (4) 2 (4) 4 (8) 4 (8) 8 (16) ↵a MHB-A, MHB with concentrations of Ca2+ and Mg2+ of 25 and 12.5 mg/liter, respectively; MHB-B, MHB with concentrations of Ca2+ and Mg2+ of 50 and 25 mg/liter, respectively; MHB-C, MHB with concentrations of Ca2+ and Mg2+ of 125 and 62.5 mg/liter, respectively; MHB-D, MHB with concentrations of Ca2+ and Mg2+ of 250 and 125 mg/liter, respectively.
- Table 4.
Influence of human urine on the in vitro activities of ciprofloxacin (CPFX) and sparfloxacin (SPFX) against E. coliNIHJ JC-2 and P. aeruginosa ATCC 27853
Subject no. NH4Cl treatment NaHCO3 treatment pH Concn [mg/liter (fold increase)] of: MIC [μg/ml (fold increase)] for: pH Concn [mg/liter (fold increase)] of: MIC [μg/ml (fold increase)] for: Ca2+ Mg2+ E. coli NIHJ JC-2 P. aeruginosa ATCC 27853 Ca2+ Mg2+ E. coli NIHJ JC-2 P. aeruginosa ATCC 27853 CPFX SPFX CPFX SPFX CPFX SPFX CPFX SPFX 1 5.36 320 (4) 145 (4.3) 0.25 (4) 0.25 (4) 0.125 2 (2) 6.28 86 61 0.063 0.063 0.50 (2) 1 2 5.40 220 (4) 120 (1.2) 0.125 (4) 0.125 (4) 0.125 (1) 2 (4) 6.37 58 100 0.031 0.031 0.125 0.50 3 5.27 200 (2) 80 0.50 (8) 0.50 (8) 0.125 (2) 2 (4) 6.10 97 105 (1.3) 0.063 0.063 0.063 0.50 4 6.39 200 (2) 135 (2.5) 0.063 (4) 0.063 (4) 0.25 (2) 0.50 (4) 7.78 43 53 0.016 0.016 0.125 0.125 5 6.03 240 (2) 145 (1) 0.125 (2) 0.25 (4) 0.125 2 (4) 7.28 225 110 0.063 0.063 0.50 (4) 0.50 6 6.12 200 (2) 54 (1) 0.50 (8) 0.50 (8) 0.25 (1) 2 (1) 7.14 13 44 0.063 0.063 0.25 2 7 6.13 270 (7) 130 (1.3) 0.125 (1) 0.25 (1) 0.25 (1) 2 (1) 7.43 41 100 0.125 0.25 0.25 2 8 5.79 80 (1) 70 (1) 0.125 (2) 0.125 (2) 0.25 1 (2) 6.35 79 85 0.063 0.063 0.50 (2) 0.50 9 5.30 56 (1) 33 (2) 0.50 (31) 0.50 (31) 0.50 (1) 2 (4) 8.01 36 18 0.016 0.016 0.50 0.25 Mean (SD) 5.75 (0.43) 178.4 (97) 101.3 (40.1) 6.97 (0.71) 75.3 (58.6) 75.1 (30.5) Range 5.27–6.39 56–320 33–145 0.063–0.50 0.063–0.50 0.125–0.50 0.50–2 6.84–8.1 13–225 18–110 0.016–0.125 0.016–0.25 0.125–0.50 0.125–2
