Voltammetric determination of penicillin V in pharmaceutical formulations and human urine using a boron-doped diamond electrode.

Simple, sensitive and selective differential pulse voltammetric method for determination of penicillin V on a bare (unmodified) boron-doped diamond electrode has been developed. Penicillin V provided highly reproducible and well-defined irreversible oxidation peak at very positive potential of +1.6V (vs. Ag/AgCl). The optimum experimental conditions for oxidation of penicillin V were achieved in acetate buffer solution (pH 4.0). The modulation amplitude of 0.1V, modulation time of 0.05s and scan rate of 0.05Vs(-1) were selected as optimum instrumental parameters for differential pulse voltammetry. Linear response of peak current on the concentration in the range from 0.5 to 40µM with coefficient of determination of 0.999, good repeatability (RSD of 1.5%) and detection limit of 0.25µM were observed without any chemical modifications and electrochemical surface pretreatment. The effect of possible interferents such as stearic acid, glucose, urea, uric acid and ascorbic acid appeared to be negligible which evidently proved the good selectivity of method. The practical analytical utility of proposed method was demonstrated by determination of penicillin V in pharmaceutical formulations (tablets) and human urine samples with satisfactory recoveries (from 98 to 101% for tablets and 97 to 103% for human urine).

Compliance with antibiotic therapy: a comparison of deuterium oxide tracer, urine bioassay, bottle weights, and parental reports.

OBJECTIVE: To compare three traditional measures of compliance with antibiotic therapy (parent report diary, preregimen and postregimen bottle-weight difference, and urine bioassay for antibiotic activity), with a deuterium oxide tracer measure of compliance. METHODS: Clinical trial in which all four compliance measures were used for subjects participating in a comparison of the efficacy of azithromycin and penicillin in treating group A beta-hemolytic streptococcal infection. Subjects were 41 children, aged 3 to 15 years (average age, 7.9 years), in a suburban pediatric private practice, who had positive rapid streptococcal antigen test results. RESULTS: Of the 41 subjects, 20 children were randomly assigned to receive azithromycin and 21 to receive penicillin. Compliance was uniformly high by all four measures. Parent diaries indicated that all doses were administered. Urine bioassays were obtained for 40 subjects, and all showed antibiotic activity. Differences in bottle weights were obtained for 27 subjects and showed that 142% of the prescribed medication was missing from the bottles at the end of the regimen. The deuterium oxide measure was obtained for 40 subjects and showed that 107% of the prescribed azithromycin and 92% of the prescribed penicillin were ingested. The correlation coefficient between measured and expected deuterium enrichment was 0.89. There was no significant correlation between the bottle-weight measure and the deuterium oxide tracer. CONCLUSIONS: The bottle-weight measure overestimates compliance; the deuterium oxide tracer is feasible for use in an office setting and produces a high correlation between the expected urinary enrichment and the measured enrichment. Increased use of this quantitative and direct measure would improve the accuracy of compliance measurement in trials of pediatric liquid medications.

Bioavailability of a new liquid formulation of penicillin V (Isocillin syrup) and the influence of ethanol on bioavailability of penicillin V.

In an open, randomized four-way crossover study, four different formulations of penicillin V each containing 1.2 mega units were tested: A) new liquid formulation of Isocillin syrup, B) new liquid formulation of Isocillin syrup plus ethanol, C) commercially available penicillin V syrup containing ethanol as solubilizer and D) Isocillin film tablets. Six male and eight female healthy volunteers participated in the study. Serum concentration and urinary excretion of penicillin V were measured by HPLC or bioassay. The new liquid formulation of Isocillin syrup showed highest Cmax and AUC values. Correspondingly, urinary excretion of the new liquid formulation of Isocillin syrup was highest (38% of the given dose). Mean pharmacokinetic data of the new liquid formulation of Isocillin syrup were: tmax (h) = 0.81, Cmax (mg/l) = 9.92, AUC0-8h (mgh/l) = 13.67, lambda z (h) = 0.68, Cltot/f (ml/min) = 964. Ethanol (4.6%) had no absorption-enhancing effects. From a clinical point of view, all four formulations investigated in this trial showed serum concentrations well above bactericidal concentrations (greater than 1 mg/l) for more than 3 h. Although the interindividual variability of serum levels was high, the levels observed would guarantee therapeutic efficacy against penicillin sensitive bacterial strains.

Ethanol and the absorption of oral penicillin in man.

The effect of alcohol on the pharmacokinetics of phenoxymethylpenicillin was studied in six healthy volunteers. Ethanol had no influence on peak penicillin serum concentrations, times of the penicillin peaks, elimination half-lives (t1/2), AUC0-8h values and 24-h urinary excretion.

Penicillin V for group A streptococcal pharyngotonsillitis. A randomized trial of seven vs ten days' therapy.

The effect of duration of orally administered penicillin V potassium on the bacteriologic and clinical cure of group A streptococcal pharyngitis was evaluated. One hundred ninety-one middle-class patients received either seven days (96 patients) or ten days (95 patients) of therapy. Compliance with taking penicillin was assessed by multiple methods, including penicillinuria. Throat cultures were obtained during therapy and three times in the three weeks after therapy. M-precipitin and T-agglutinin typing were done on paired isolates of group A streptococci from patients who had recurrences. Patients treated for seven days had a significantly greater failure rate (30/96 [31%]) compared with patients receiving ten days of penicillin (17/95 [18%]). Compliance rates were high; 66% to 81% of patients showed penicillinuria throughout the study period. Treatment failure was not a function of poor compliance in either treatment group. The data support the current recommendation for ten full days of penicillin therapy and suggest that persistence of streptococci in the throat after adequate therapy may be common.

Urine concentrations of five penicillins following oral administration to normal adult dogs.

Penicillin G, penicillin V, ampicillin, hetacillin, and amoxicillin were administered separately per os to clinically normal adult dogs of both sexes at 8-hour intervals for five consecutive 8-hour test periods. All urine was collected from each dog during each test period and was assayed for antimicrobial activity. Daily doses of the antimicrobics used were as follows: penicillin G, 110,000 U/kg of body weight; penicillin V, 77 mg/kg; ampicillin, 77 mg/kg; hetacillin, 77 mg/kg; and amoxicillin, 33 mg/kg. Mean 8-hour urine concentrations (+/- 1 SD) were as follows: penicillin G, 294 +/- 210 U/ml; penicillin V, 148 +/- 98 micrograms/ml; ampicillin, 309 +/- 55 micrograms/ml; hetacillin, 300 +/- 156 micrograms/ml, and amoxicillin 201 +/- 93 micrograms/ml. Among the three antimicrobials administered at the same daily dosage, ie, penicillin V, ampicillin, and hetacillin, the mean urine concentrations of penicillin V were significantly lower (P < 0.01) than were concentrations of ampicillin and hetacillin. The mean urine concentrations of the latter two did not differ significantly (P > 0.05).