Kinetics of talampicillin decomposition in solutions.

Talampicillin stability in aqueous solutions was studied in a broad range of pH values using as medium solutions of hydrochloric acid (pH 0.4-1.8), phosphate buffers (pH 2.05-3.13 and 6.03-8.04), acetate buffer (pH 3.87-5.28) and borate buffer (pH 8.90-9.10) as well as sodium hydroxide solution (pH 11.48). For the determination of talampicillin concentration changes in kinetic studies, two methods were used: iodometric and spectrophotometric in UV (lambda(max) = 254.5 nm). The catalytic velocity constants (k(H+), k(x), k(o)) were established, the log k-pH profile (35 degrees C) was found, thermodynamic parameters were calculated of the hydrolysis reaction of the beta-lactam bond (k(H+): E(A)= 67.9 kJ mol(-1), delta S = -92.4 J K(-1) mol(-1), delta G = 92.6 kJ mol(-1); k(x): E(A) = 31.8 kJ mol(-1), delta S = -347.1 J K(-1) mol(-1), delta G = 131.1 kJ mol(-1); k(o), pH = 5.28: E(A) = 98.0 kJ mol(-1), delta S = -50.3 J K(-1) mol(-1), delta G = 110.3 kJ mol(-1) at 20 degrees C), and the stability of the lactone bond was studied in the medium with the highest stability of beta-lactam bond of talampicillin (pH 5.28: k(o): E(A)= 32.5 kJ mol(-1), delta S = -220.5 J K(-1) mol(-1), delta G = 94.7 kJ mol(-1) in 20 degrees C), at controlled ionic strength (mu = 0.5 mol l(-1)).

Evaluation of oral antimicrobial agent levels in tooth extraction sites.

OBJECTIVE: The purpose of this study was to evaluate various oral antimicrobial agent levels in tooth extraction sites. STUDY DESIGN: The concentration of dental alveolar blood in extraction wounds after the oral administration of talampicillin (500 mg), cefaclor (500 mg), cefteram pivoxil (200 mg), cefuroxime axetil (250 mg), cefdinir (200 mg), and ofloxacin (100 mg) was determined in 338 patients and was assessed on the basis of its antimicrobial activity against Streptococcus isolated in odontogenic infections. RESULTS: The percentage of patients whose concentrations exceeded the minimum inhibitory concentration for 90% of Streptococcus was 62.5% to 100% for talampicillin at 30 to 360 minutes, 0% to 12.5% for cefaclor at 30 to 360 minutes, 18.2% to 100% for cefteram pivoxil at 30 to 480 minutes, 50% to 100% for cefuroxime axetil at 30 to 480 minutes, 0% to 50% for cefdinir at 16 to 290 minutes, and 0% to 40% for ofloxacin at 30 to 480 minutes. CONCLUSION: These results indicate that talampicillin, cefteram pivoxil, and cefuroxime axetil have minimum inhibitory concentration levels for 90% of Streptococcus in tooth sockets.

Oral bioavailability and in vitro stability of pivampicillin, bacampicillin, talampicillin, and ampicillin in horses.

OBJECTIVES: To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5). DESIGN: A crossover design to administer the 4 drugs orally, and ampicillin i.v. to all horses in the study. ANIMALS: 4 healthy adult horses. PROCEDURE: The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered i.v. at the same dosage. Blood samples were taken up to 12 hours after drug administration, and ampicillin concentrations in plasma were determined. For the in vitro study, the ampicillin esters were incubated at 37 C in ileal contents obtained from ponies with cecal fistulas. After incubation, the remaining intact ester and the formed ampicillin were measured. RESULTS: Absolute oral bioavailability was 31, 39, 23, and 2% for pivampicillin, bacampicillin, talampicillin, and ampicillin sodium, respectively. In the in vitro study, 90% decomposition of the ester took place in 30, 60, and 5 minutes, for pivampicillin, bacampicillin, and talampicillin, respectively. CONCLUSIONS: Pivampicillin and bacampicillin are promising candidates for oral antibiotic treatment of horses. The rapid decomposition of ampicillin esters is caused by chemical hydrolysis at the high pH of equine ileal contents.

Drug eruptions following treatment with prodrugs: a review of the reported cases in Japan from 1984 to 1989.

A review of 872 cases of drug eruption reported in the Japanese dermatological journals from 1984 to 1989 has revealed a growing subset related to treatment with prodrugs, in which the responsible agent may be the metabolite rather than the prodrug itself. This situation is the result of the presence in tissues and fluids of only the metabolite following absorption and degradation of the prodrug. Because of this condition, patients with drug eruptions after prodrug treatment may develop positive patch test and/or lymphocyte stimulation test reactions not only with the introduced prodrug but also with the metabolite produced in vivo and further with other prodrugs which degrade into the same metabolite.

Potential improvement in the shelf life of parenterals using the prodrug approach: bacampicillin and talampicillin hydrolysis kinetics and utilization time.

The utilization time for a parenteral prodrug solution with a bioavailable fraction of unity was defined as the time during which the total of the prodrug concentration and the drug concentration equals or exceeds 90% of the initial prodrug concentration. This utilization time was calculated as a function of pH, buffer, and temperature using the experimentally determined rate expressions for bacampicillin and talampicillin. The results were compared to the shelf life of ampicillin solutions under identical storage conditions. First-order rate constants were determined for conversion of the prodrugs to ampicillin (kc), for beta-lactam degradation of the prodrugs (knc), for the overall loss of prodrugs (ksum), and for beta-lactam degradation of ampicillin (kh) in aqueous solutions at 25.0 to 60.0 degrees C, mu = 0.5, in the pH range 0.90 to 8.4. Loss of bacampicillin proceeded primarily by degradation at pH levels below 4 but was due predominantly to conversion at pH levels above 5. Loss of talampicillin was due primarily to conversion throughout the entire pH range. While the prodrug utilization times were approximately twice the shelf life of ampicillin in acidic solutions, ampicillin was significantly better in neutral solutions. The results illustrate the potential for increased prodrug storage periods when utilization time is defined on the basis of the bioactivity rather than on the prodrug concentration alone.

Ampicillin concentrations in human dental granuloma after a single oral administration of talampicillin.

Ampicillin concentrations in human serum and dental granulomas of 31 patients were determined after a single oral dose of talampicillin (equivalent to 500 mg of ampicillin) was administered to each. The specimens were taken at 1.5, 2.0, 2.5, 3.0, and 3.5 h after the administration of talampicillin. The mean peak ampicillin concentrations in serum and dental granulomas occurred at identical times, 2.5 h, and were 8.29 micrograms/ml (range, 1.81 to 13.20 micrograms/ml) and 2.94 micrograms/g (range, 1.14 to 7.16 micrograms/g), respectively. The mean dental granuloma/serum ampicillin concentration ratio at the peak time (2.5 h) was 0.42 (range, 0.29 to 0.56). Ampicillin concentrations in dental granulomas exceeded most of the MICs for the bacteria commonly isolated from odontogenic infection.

Ampicillin concentrations in human serum and periodontal membrane following a single oral administration of talampicillin.

1. Ampicillin concentrations in human serum and periodontal membrane after a single oral administration of talampicillin (500 mg) were assayed by the agar diffusion (paper disc) method. 2. The peak times of serum and periodontal membrane were identical, being 150 min after administration. 3. The peak concentrations of serum and periodontal membrane were 7.81 micrograms/ml and 4.11 micrograms/g, respectively. 4. The mean ratio of periodontal membrane to serum concentration at the peak time was 0.53.

Bacampicillin, amoxycillin and talampicillin concentrations in bronchial secretions.

There are references in the literature describing the influence of bronchial inflammation on the antibiotic concentration in bronchial secretions, including netilmicin concentrations in the bronchial secretion of patients undergoing tracheotomy. Three semi-synthetic penicillins are compared--bacampicillin, amoxicillin and talampicillin--administered frequently in the treatment of various respiratory infections. The three antibiotics were administered successively for two days each, in the same patient, irrespective of other drugs. At the same time the cytologic evaluation of the degree of bronchial inflammation was done. The antibiotic concentrations in bronchial secretions and in sera were measured at the same time. The results showed that the concentration of antibiotics in bronchial secretions of patients undergoing tracheotomy was proportional to the degree of bronchial inflammation. Among the semi-synthetic penicillins investigated the highest degree of concentration in the bronchial secretion was obtained after the bacampicillin.

Liquid chromatographic determination of ampicillin and its metabolites in human urine by postcolumn alkaline degradation.

A high-performance liquid chromatographic method has been developed for the determination of ampicillin (I) and its metabolites [5R,6R)-penicilloate (II), the (5S,6R)-epimer (III), and piperazine-2,5-dione (IV)) in human urine. The assay was based on the measurement of the absorbance at 300 nm following the postcolumn alkaline degradation with 0.75 M sodium hydroxide, 2 X 10(-3) M mercuric chloride, and 1 X 10(-2) M ethylenediaminetetraacetic acid disodium salt in solution. The limits of accurate determination were 0.5 microgram mL-1 for I, 2.0 microgram mL-1 for II and III, and 1.0 microgram mL-1 for IV in neat urine samples with a 10 microL injection. At concentrations of compounds I-IV of 5 micrograms mL-1, within- and between-run precisions were 1.10-4.03% and 0.93-2.34%, respectively. The urinary levels of I and its metabolites were quantified by the proposed method.

Blood levels and distribution of talampicillin and bacampicillin in NZW rabbits.

Parameters for blood concentrations of the peroral antibiotics talampicil in and bacampicillin, in NZW rabbits were determined using a two compartment model. On the basis of these pharmacokinetic parameters, a three compartment model was prepared for the concentrations of these drugs in the tongue, gingiva, submandibular gland, parotid gland, cervical lymph-node and mandibular bone. Simulation curves based on the parameters of tissue concentrations revealed visual conformity to the measured values.

Effect of beta-lactam prodrugs on human intestinal microflora.

The ampicillin prodrugs bacampicillin, pivampicillin, and talampicillin, the mecillinam prodrug pivmecillinam and the sulbactam prodrug sulbactam pivoxil all have a greatly improved oral availability compared to the parent drug. They show no antibacterial activity themselves until transformed into active drugs after absorption. This double advantage makes them less likely to influence the intestinal microbial ecosystem. Ampicillin has been reported to cause marked changes in the colon microflora, particularly as regards Enterobacter species, Klebsiella species, enterococci, lactobacilli, bacteroides, and clostridia, in contrast to pivampicillin, which did not exert much influence. Similarly, talampicillin has been reported to have less influence than ampicillin on the colon flora. Diarrhoea was more common after ampicillin and was accompanied by an overgrowth of Candida. Pivmecillinam has been reported to reduce the number of Escherichia coli and lactobacilli. No changes were seen in the colon flora of subjects receiving bacampicillin tablets. This was verified in a parallel group study, in which one group was given the combination of bacampicillin and sulbactam pivoxil, the other bacampicillin, for seven days. Of the subjects given the combination, five had a moderate and ten a considerable change in their colon microflora. The subjects were often heavily colonized by new aerobic strains such as enterococci, E. coli, Bacillus, Enterobacter, Aeromonas, and yeasts. Among the anaerobes, Veillonella, the bifidobacteria-lactobacillus group, and bacteroides decreased. Some strains of clostridia decreased but there was also a colonization with new strains. One subject was colonized with Clostridium difficile. Diarrhoea was seen only during the week of active drug administration in the group given the combination. The symptoms generally appeared on the second or third day of treatment and had, in most cases, subsided at the end of treatment. The results illustrate the correlation between disturbances in the intestinal microbial ecosystem and intestinal adverse reactions.

[A comparative double blind study of lenampicillin and talampicillin in the treatment of oral infections].

A comparative double blind study of lenampicillin (LAPC, KBT-1585) and talampicillin (TAPC) was carried out in order to objectively evaluate efficacy, safety and utility of LAPC in treatment of 238 patients with oral infections. Cases accepted by the Central Committee for evaluation of efficacy and utility were 218, consisting of 101 of the LAPC group and 117 of the TAPC group; safety were 234, consisting of 110 of LAPC and 124 of TAPC. Clinical effectiveness as rated by attending doctor was 84.2% for the LAPC group and 82.9% for the TAPC group. The clinical utility rating was 82.2% in the LAPC group and 82.1% in the TAPC group, showing no significant difference between the 2 drugs. Adverse reactions were found in 6 cases (5.5%) in the LAPC group and 5 cases (4.0%) in the TAPC group, showing no significant difference between the 2 drugs. Cases accepted by the controllers for evaluation of efficacy and utility were 236, consisting of 111 cases of LAPC and 125 cases of TAPC. Those for safety were 236, consisting of 111 cases of LAPC and 125 of TAPC. The clinical effectiveness rating was 77.5% in the LAPC group and 79.2% in the TAPC group. Clinical utility rating was 75.7% in the LAPC group and 78.4% in the TAPC group. Rate of adverse reactions was 5.4% in the LAPC group and 4.0% in the TAPC group, showing no significant difference between the 2 drugs. Cases evaluated for efficacy according to numerical rating on the 3rd day were 200 cases, consisting of 93 of LAPC and 107 of TAPC. The effectiveness rate was 83.9% in the LAPC group and 95.3 in the TAPC group, showing a significant difference between the 2 drugs. On the other hand, taking into consideration evaluation scores of the 5th day, the effectiveness rate was 88.7% in the LAPC group and 96.1% in the TAPC group, showing no significant difference between the 2 drugs. The effectiveness rate in cases of isolated organisms was 84.9% in the LAPC group and 79.7% in the TAPC group, showing no significant difference between the 2 drugs. Adverse reactions were mostly of gastrointestinal origin. Symptoms were not serious and disappeared soon after administration was discontinued or immediately after administration was completed.(ABSTRACT TRUNCATED AT 400 WORDS)

[The duration of antibacterial treatment following transurethral prostatectomy].

Forty-three cases were studied to determine the most optimal timing to discontinue an oral antibacterial agent for preventing urinary tract infection after transurethral prostatectomy. On the 5th postoperative day intravenous antibiotic treatment was replaced by oral medication of 1.5 g talampicillin hydrochloride (TAPC, Yamacillin), which was tapered and discontinued depending on the urinary findings. Nine out of 15 cases who discontinued the medication within 2 weeks failed to keep the urine sterile. It may be advisable to continue the medication at least 3 weeks and to discontinue thereafter when pyuria has vanished. All 24 cases who followed this principle became sterile within 8 weeks. Medication continued over 8 weeks seemed to have no additional benefit. Four cases dropped out from this treatment mainly because of gastrointestinal symptoms.

Ampicillin concentrations in human serum, gingiva, mandibular bone, dental follicle, and dental pulp following a single oral dose of talampicillin.

Eighty-one patients who underwent the extraction of impacted mandibular third molars in the nonfasting state were given a single oral dose of talampicillin (500 mg) preoperatively. Specimens of venous blood (n = 132), gingiva (n = 70), mandibular bone (n = 78), dental follicle (n = 63), and dental pulp (n = 59) were obtained during the operation and assayed for ampicillin content. The mean peak concentrations in serum (9.64 micrograms/ml), gingiva (4.72 micrograms/mg), mandibular bone (1.77 micrograms/ml), dental follicle (3.46 micrograms/ml), and dental pulp (5.53 micrograms/mg) all occurred at approximately 150 minutes after administration of talampicillin. The ratios of the corresponding serum concentration to the peak concentrations in the various oral tissues when both were plotted as drug concentration curves were: gingiva, 0.50; mandibular bone, 0.16; dental follicle, 0.34; and dental pulp, 0.52. Talampicillin was absorbed well by the intestine, and sufficient concentrations of the resulting metabolite, ampicillin, were found in oral tissues.

Concentrations of ampicillin and cefadroxil in human serum and mixed saliva following a single oral administration of talampicillin and cefadroxil, and relationships between serum and mixed saliva concentrations.

The concentrations of ampicillin (ABPC) from talampicillin (TAPC) and cefadroxil (CDX) in serum and mixed saliva were assayed by the thin layer disc plate method. Talampicillin and cefadroxil (500 mg) were given by a single oral administration. The relationships between serum and mixed saliva ampicillin and cefadroxil concentrations were evaluated in the paired specimens collected from 10 different persons, respectively. The means of concentration ratios of mixed saliva to serum ampicillin and cefadroxil were 0.006 +/- 0.003 and 0.025 +/- 0.010 (mean +/- SD), respectively. Significant correlation coefficients between mixed saliva and serum concentrations were found for both ampicillin and cefadroxil, which were r = 0.78, P less than 0.001, and r = 0.67, P less than 0.001, respectively.

Tre atment of Gonorrhoea with Antibiotic Combinations : Kanamycin plus Ampicillin / Probenecid versus Kanamycin plus Talampicillin / Probenecid / 대한피부과학회지

riie snbjects werc 269 patients with uncomplicated gonococcal urethritis, who visited the Veiereal Disease Clinic of Choong-Ku Public Health Center in Fieoul from August to Decernber 1984. ()ni hundred and four of 108 patients treated with 1.anamycin, 2 gm, IM plus anipi illin,3.5 gm, p0 plus probenecid, 1 gm, PO regirrien recovered with 65(62. 5 post-gonococcal urethritis(PGlJ) and 4(3.7%) failed, One hundred and seven of III patients treated with kanamycin, 2 gm, IM plus talarnpicillin, 2 gm, PO plus probenecid, 1 gm, po regimen recovered with 71 (66. 4% ) post-goriococcal urethritis and 4(3. 6%) failed. It is suggeste,d that both these antibiotic comlbination regimens have similarly good effect in the treatment. of gonococcal urethritis.

The Effect of Combination Therapy of Kanamycin Plus Talampicillin for Uncomplicated Male Gonorrhea / 대한피부과학회지

The treatment of gonorrhea caused by beta-strains of N. gonorrhoeae is quite different from that of non-beta-strains, but it is not always possible in general practice to take cultures of gonococci to detect p-lactamase producing organisms. Therefore treatment regimens commonly used for gonorrhoea should be effective against both PPNG non-PPNG strains. Eighty-seven male uncomplicated gonorrheal patients were treated with intramuscular kanarnycin 2gm in combilnation with talampicillin 2. 5 gm plus probenecid 1grn orally. Sixty-seven patients were followed up. All patients recovered. Ten patients among sixty-seven patients had PPNG. A regimen of intramuscular kanamycin 2 gm, talampicillin 2. 5 gm plus probenecid 1 0 gm orally seems to be one of the most cost effective regimens in Korea.

Clinical Study of Pharyngeal Gonorrhea / 대한피부과학회지

Five hundred seventeen male patients with gonococcal urethritis at the VD clinic of Chocng-ku Public Health Center between Feb. 27 and Oct. 27, 1984 the were source cf this study. Forty-five of seventynine patients who had practiced cunnilingus were actual subjects of this study. Aeiss.ria gonorrhoeae were cultured from the pharynx of five patients: one was found to be PPNG. All 5 pharyngeal gonorrhea patients were asymptornatic and their throat appeared to be normal, except injection of the pharynx in one patient. Two patients infected by non-PPNG were administered an oral dose of 1. 0 gm probenecid plus 2 5 gm talampicillin and 2. Ogm Kanamycin sulfate, IM and one patient infected by non-PPNG was administred an oral dose of l. Ogm probenecid and, 3i) minutes later, 6. 0 m.u. fortified procaine penicillin G IM. One gatient infected by PPNG was administered an oral dose of 1, 0 gm probenecid and 30 minutes later, 1 vial of sulbactam sodium/ampicillin sodium, IM. All four pharyngeal gonorrgeal patients were cured, One patient was lost from further evaluation, We consider it important to have pharyngeal cultures done on all gonorrheal patients, at least on those who admit having had orogenital contact in recent episode, because pharyngeal gonococci may be the source of disseminated gonococcal disease and in rare circumstances, the source of mfection for sexual partners, and single lose spectinomycin and orally administered penciillin regimens that are effective against anogenital gonorrhea, had been known to have high rates of failure when used in the pharyngeal gonrorhea.