Evaluation of tetracycline in milk following extra-label administration of topical tetracycline for digital dermatitis in dairy cattle.

Digital dermatitis (DD) is a painful infectious foot lesion commonly treated topically with extra-label tetracycline. Our objectives were to determine the concentrations of tetracycline in milk and plasma and to calculate a withdrawal interval following topical application at various doses. Another objective was to evaluate agreement between tests for measuring tetracycline in milk. A randomized block trial was conducted on 2 farms, where 50 cows with active DD lesions on 2 feet were allocated to 1 of 5 treatment groups (n = 10 cows per group). Treatment groups consisted of topical applications of tetracycline hydrochloride, in a paste or as a powdered form under a bandage, at 3 different dosing levels (2, 5, and 25 g) on each of the 2 affected feet. Following enrollment and treatment, samples were collected from milk, teat skin, and blood every 8 to 24 h for up to 7 d postdosing. Concentrations of tetracycline were measured by liquid chromatography-mass spectrometry and milk samples were further tested using the Charm ROSA TET test (Charm Sciences Inc., Lawrence, MA). Tetracycline was present in milk, plasma, and teat skin from all treatment groups. Tetracycline concentrations varied depending on time of sampling, method of application, and dosing level. At 8 h post-treatment, 11% of cows had tetracycline present in milk higher than 100 ng/mL (ppb) but none higher than 300 ng/mL. The 25-g treatment group had the longest estimated withdrawal interval, the highest observed concentrations (210-244 ng/mL) of tetracycline present in milk, and the longest observed consecutive period of tetracycline presence (from 8 to 72 h) among all treatment groups. Compared with liquid chromatography-mass spectrometry, the Charm test had a sensitivity of 77 and 100% for measuring tetracycline in milk at ≥30 and ≥100 ng/mL, respectively. Post-treatment samples of the teat skin were taken from 15 cows on 6 occasions, and every cow had tetracycline present in at least 1 of those 6 samples. This confirms an association between topical DD treatment with tetracycline and contamination of the teat. A total of 22% of blood samples had detectable tetracycline, and the majority (63%) occurred at 8 h post-treatment. At 100 ng/mL, the estimated cow-level milk withdrawal interval ranged from 0 to 70 h. At 300 ng/mL, the estimated cow-level withdrawal interval ranged from 0 to 34 h, and was 0 h at the bulk tank level. We recommend that conservative measures be adopted after extra-label use of topical tetracycline for DD treatment, including using a low dose and strategic post-treatment testing for tetracycline-class drugs in milk.

Effect of a Kampo preparation, byakkokaninjinto, on pharmacokinetics of ciprofloxacin and tetracycline.

The effect on the bioavailability of the antimicrobial agents (ciprofloxacin and tetracycline), which are well known to form chelates with cationic metals such as calcium, was evaluated in 20 healthy male volunteers according to an open, random crossover fashion using a Kampo preparation, byakkokaninjinto (TJ-34) which contains various cationic metals including calcium. Each subject received a single oral dose of tetracycline (250 mg) alone or ciprofloxacin (200 mg) alone along with a single coadministration of one pack (3 g) of the Kampo preparation, at one-week intervals. Concentrations of the drugs in plasma and urine were analyzed by HPLC. Concomitant administration of the Kampo preparation significantly decreased the peak plasma concentration (C(max)) and area under the plasma concentration-time curves (AUC), but not time to reach C(max) (T(max)), of ciprofloxacin and tetracycline. However, the decrease in bioavailability of ciprofloxacin was slight (15%) compared with that of tetracycline (30%). The Kampo preparation significantly decreased the urinary recovery of tetracycline, but not ciprofloxacin, and it had no effect on the renal clearance of either ciprofloxacin or tetracycline. These results indicate that the Kampo preparation tested in this study reduces the extent of bioavailability of ciprofloxacin and tetracycline, but not renal excretion, by decreasing the gastrointestinal absorption due to the formation of insoluble chelates with calcium. We recommend that the dose timing of the Kampo preparation should be carefully controlled to avoid therapeutic failure especially for patients receiving the treatment with tetracycline.

Effect of oral tetracycline on iron absorption from iron(III)-hydroxide polymaltose complex in patients with iron deficiency anemia / a single-centre randomized controlled isotope study.

The study was carried out as an open-label, laboratory-blind, single-dose, randomized, two-period crossover, isotope efficacy study. Twenty-two patients with iron-deficiency anemia were enrolled in the study. The study consisted of two treatment phases of 15 days each, including blood sample measurements for Fe-59 activity. The two treatments were given orally. Treatment A was Fe-59 labeled iron(III)-hydroxide polymaltose complex (IPC, Maltofer) equivalent to 100 mg elemental iron given orally. Treatment B consisted of Fe-59 labeled IPC complex equivalent to 100 mg elemental iron and 500 mg tetracycline HCl (CAS 64-75-5) given orally. No differences between the two treatment groups with regard to the erythrocyte iron uptake were found, and thus IPC can be used with tetracycline, if necessary.

Efficacy of a novel tetracycline derivative, glycylcycline, against penicillin-resistant Streptococcus pneumoniae in a mouse model of pneumonia.

The MIC90 of glycylcycline (< or =0.06 mg/L) against 55 strains of Streptococcus pneumoniae was 100-fold lower than that of minocycline or tetracycline. In a mouse model of penicillin-resistant S. pneumoniae (PRSP) pneumonia, glycylcycline (10 mg/kg) decreased bacterial counts in the lungs from 10(6) cfu to <10(2) cfu, whereas no apparent reduction of bacterial numbers was observed with minocycline or penicillin G. Pharmacokinetic studies showed that the half-life and area under the curve of glycylcycline were superior to those of minocycline and penicillin G in the lungs. These results show a preferential distribution of glycylcycline in the lungs and potent in vivo bactericidal activity in PRSP pneumonia.

Targeting of Wolbachia endobacteria in Litomosoides sigmodontis: comparison of tetracyclines with chloramphenicol, macrolides and ciprofloxacin.

Endobacteria of the genus Wolbachia in filarial nematodes are related to Rickettsiaceae and can be depleted by tetracycline antibiotics. This depletion blocks female worm development as well as early embryogenesis, in contrast to the currently used microfilaricidal ivermectin which blocks only the last stage of embryogenesis. Since targeting Wolbachia is becoming an area of research for the treatment of human filariases, it was investigated if antibiotics other than tetracyclines are able to deplete Wolbachia from filariae. BALB/c mice infected with the rodent filaria Litomosoides sigmodontis were treated with erythromycin, chloramphenicol or ciprofloxacin. All drugs were well resorbed and resulted in serum levels clearly above breakpoint levels for bacteria susceptible to the respective antibiotic. However, contrary to tetracycline, none of these antibiotics depleted Wolbachia or altered worm development and fertility, as evidenced by immunohistology, immunoelectron microscopy and semiquantitative PCR.

Efeitos da N-(Pirrolidino-Metil): tetraciclina sobre o sangue da preá (Cavia Aperea Aperea) Erxleben-1777 (Rodentia) / Effect of the pirrolidino-metil-tetracycline upon o blood of preá Cavia Aparea Aparea

Na presente pesquisa estudou-se os efeitos da tetraciclina sobre o teor de cálcio sanguíneo e a influência da droga no tempo de coagulação

[Bioavailability of tetracycline hydrochloride capsules (an in vivo study)]. / Biodostupnost' kapsul tetratsiklina gidrokhlorida (issledovanie in vivo).

Blood absorption of tetracycline hydrochloride of various dispersity levels from capsules containing tetracycline alone or in combination with additives, such as magnesium carbonate and calcium salts was studied on humans. It was found that higher dispersity levels of tetracycline hydrochloride powder in capsules was not accompanied by increased blood absorption of the antibiotic. Addition of magnesium carbonate and calcium salts to the antibiotic in the process of capsulation markedly retarded the blood absorption. Clear correlation between the antibiotic dissolution rate in vitro and intensity of its blood absorption in volunteers was shown.

Sustained action tetracycline preparation--tetrabid-organon blood level study.

A comparison of the plasma levels of tetracycline obtained whilst taking standard therapeutic doses of Tetrabid-Organon was made in twelve healthy volunteers. Two standard production batches were used in the study which was conducted under double-blind conditions. Sampling 12 hours and 8 hours after dosing showed no significant differences in plasma levels, with each batch. Even at these lowest levels satisfactory concentrations were rapidly obtained following initial administration, and were maintained when the drug was given at 12-hourly intervals. No side-effects of the drug were noted.

Tetracycline in the treatment of uncomplicated male gonorrhea.

A clinical trial was performed to test a loading dose regimen of tetracycline (1.5 gm po sTAT and 0.5 mg po quid for 4 days) against a no-loading dose (0.5 gm po quid for 4 1/2 days) in the treatment of 477 cases of uncomplicated male urogenital gonorrhea. The regimens were equivalent, with an overall cure rate of 96%. A crossover pharmacokinetic study in 10 healthy volunteers demonstrated higher blood levels during the first day on the loading regimen, but equivalence thereafter. Tetracycline, in a total dose of 9.5 gm, is highly effective treatment, and a loading dose is not necessary.