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.

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.

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.

Bioavailability of bacampicillin and talampicillin, two oral prodrugs of ampicillin.

A 200-mg amount of bacampicillin showed a significantly higher relative extent of bioavailability than did a 250-mg amount of talampicillin, possibly due to their different stability in the digestive juices.

The metabolism of talampicillin in rat, dog and man.

1. After administration of [phthalidyl-14C] talampicillin (Talpen) to rat, dog and man, radioactivity was excreted mainly in the urine (90%, 86% and 98% in rat, dog and man respectively). 2. After administration of [ampicillin-14C] talampicillin, radioactivity was excreted in the urine of rats and dogs to a lesser extent (35% in both species) and only a small proportion of the dose was excreted in the bile (6% in rats, less than 0.1% in dogs). 3. The pattern of radiometabolites was very similar in extracts of the urines of radiometabolites was very similar in extracts of the urines of rat, dog and man dosed orally with [phthalidyl-14C]talampicillin. The major metabolite was 2-hydroxymethylbenzoic acid. 4. Unchanged talampicillin was present in the hepatic portal vein blood of dog and thus reached the liver, whereas in rat, no parent compound could be detected in portal vein blood. This result may help to explain differences in toxicity of the compound in rat and dog. 5. Studies in vitro showed that the intestinal wall is an important site of hydrolysis of talampicillin in rat and dog.

[Talampicillin hydrochloride: Comparison with amoxicillin and ampicillin in the antibacterial activity and pharmacokinetics (author's transl)].

The antibacterial activities, absorption and excretion of talampicillin hydrochloride were compared with those of amoxicillin and ampicillin. Talampicillin hydrochloride showed a broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria as seen in amoxicillin and ampicillin. The antibacterial activities of talampicillin hydrochloride, amoxicillin and ampicillin were quite similar. In experimental murine infection with Staphylococcus aureus, protective effect of talampicillin hydrochloride was superior to ampicillin. For Escherichia coli infection, protective effect of talampicillin hydrochloride was similar to that of amoxicillin, while ampicillin was less active than both talampicillin hydrochloride and amoxicillin. The absorption and excretion of 250 mg equivalent doses of talampicillin hydrochloride, amoxicillin and ampicillin were compared in nine fasting healthy volunteers after oral administration of these antibiotics in randomized triple crossover study. In order to calculate the pharmacokinetic parameters, plasma levels were analyzed using an one-compartment open model, as well as area under the plasma concentration curve (AUC) and urinary excretion. Maximum plasma levels calculated were 2.8 times higher for talampicillin hydrochloride and 1.45 times higher for amoxicillin than for ampicillin. AUC was greater for talampicillin hydrochloride than for amoxicillin and lowest for ampicillin. Urinary excretion of talampicillin hydrochloride as penicillin determined in biological assay was comparable to that of amoxicillin and 1.55 times higher than that of ampicillin. Penicillins can be metabolized to penicilloic acids in the body. After taking into account the penicilloic acid contents in urine, total excretion in urine was 61% for talampicillin hydrochloride, 67% for amoxicillin and 42% for ampicillin during 6 hours after dosing. The absorption of the drugs was evaluated according to the plasma levels, the area under plasma concentration curve and the percentage of excretion in urine. The results obtained showed that talampicillin hydrochloride was well absorbed from the gastro-intestinal tract.

Bioavailability and metabolism of talampicillin.

Talampicillin is an ester of ampicillin which is readily hydrolysed on absorption to release ampicillin. It is well absorbed from the gastro-intestinal tract resulting in a greater bioavailiability of ampicillin than can be achieved with equivalent doses of ampicillin itself. Dose response studies have confirmed a direct relationship between the dose of talampicillin administered and peak serum ampicillin concentration and urinary excretion of ampicillin. Dosing of ampicillin after food has been shown to adversely affect the total bioavailability of ampicillin. This is not so after dosing with talampicillin. The bioavailability of ampicillin from a 250-mg Talpen tablet dosed after a large meal was significantly greater than that from 250 mg ampicillin dosed in the fasting state. Studies in volunteer subjects at multiples of the proposed therapeutic dose for periods of up to 28 days have indicated its acceptability, bioavailability and lack of side effects on repeated dosing. The fate of the phthalidyl moiety of talampicillin has been investigated in repeated dose studies and in a single dose studies and in a single dose study in which radiolabelled talampicillin was administered. The principal metabolite of the phthalidyl moiety in man has been shown to be 2-hydroxymethylbenzoic acid, which is identical to that in experimental animals used for toxicological investigations.