Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs.

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)) 4.20 +/- 1.66 microg x h/mL; C(max) 6.64 +/- 1.38 microg/mL; V(z) 4.80 +/- 0.91 L/kg; Cl(t) 2.64 +/- 0.84 L/h.kg; t((1/2)lambda) 1.35 +/- 0.40 h and MRT 1.50 +/- 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean +/- SD): C(max), 0.30 +/- 0.17 and 0.17 +/- 0.09 microg/mL; t(max), 1.75 +/- 0.76 and 0.69 +/- 0.30 h; t((1/2)lambda), 2.92 +/- 0.79 and 1.53 +/- 1.28 h and MRT, 5.10 +/- 1.12 and 2.56 +/- 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC(90) = 0.5 microg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.

Simultaneous determination of erythromycin ethylsuccinate and its metabolite erythromycin in human plasma using liquid chromatography-electrospray ionization mass spectrometry for clinical study.

A sensitive and selective liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for simultaneous identification and quantification of erythromycin ethylsuccinate and erythromycin in human plasma, which can be well applied to clinical study. The method was based on liquid-liquid extraction, followed by a LC procedure with an ODS C18 column, and mixture of acetonitrile and 1.67 mmol/l acetic acid as mobile phase. MS detection was performed using a single quadrupole mass spectrometer in positive selected ion monitoring (SIM) mode. The method was validated to be linear, precise and accurate. The lower limit of quantification of erythromycin ethylsuccinate and erythromycin were both 0.5 ng/ml. The proposed method enables the unambiguous identification and quantification of erythromycin ethylsuccinate and erythromycin for clinical drug monitoring.

Pharmacokinetics of erythromycin ethylsuccinate after intragastric administration to healthy foals.

Plasma concentrations and pharmacokinetics of erythromycin and related compounds were determined after administration of erythromycin ethylsuccinate to six healthy male foals 3 to 5 months of age. Hay was withheld from the foals overnight and erythromycin ethylsuccinate (25 mg/kg of body weight) was administered intragastrically. Plasma erythromycin concentrations were determined at specific times after drug administration by high-performance liquid chromatography assay. Maximum peak plasma concentrations, time to maximum concentrations, area under plasma concentration versus time curves, elimination half-life, and mean residence time were determined from concentration versus time curves. Maximum peak concentration of erythromycin A (0.45 +/- 0.27 microg/ml) after administration of erythromycin ethylsuccinate was observed at 2.38 +/- 1.54 hours after treatment. Concentrations of anhydroerythromycin A were maximal at 2.2 +/- 2.0 hours and reached a maximum of 2.6 +/- 1.9 microg/ml. Plasma concentrations of the ester parent drug (erythromycin ethylsuccinate) were below the limit of quantitation (0.1 microg/ml) at all times except 2.5, 2.75, and 5.5 hours. Levels at those times ranged from 0.1 to 0.144 microg/ml. Erythromycin ethylsuccinate appears to be poorly absorbed after oral administration to fasted foals. Plasma concentrations of erythromycin A remained below 0.25 microg/ml (reported minimum inhibitory concentration for Rhodococcus equi) for less than 4 hours after intragastric administration of erythromycin ethylsuccinate, suggesting that the recommended dosage (25 mg/kg every 6 hours) would be suboptimal for treatment of R. equi infections.

Prokinetic effects of erythromycin after antimotion sickness drugs.

Motion sickness and the antimotion sickness drugs scopolamine (SCP) and promethazine (PMZ) inhibit gastric emptying (GE). This study was conducted to determine if erythromycin would exert its well-known prokinetic effects in normal and motion-sick subjects given antimotion sickness drugs. Fifteen fasted volunteers (11 males, 4 females) participated in the study. In control tests, 8 subjects were given intramuscular (i.m.) saline (SAL, 0.5 ml), SCP (0.1 mg), or PMZ (25 mg). GE of liquid (300 ml) containing 1 mCi of Tc 99m diethylenetriaminepentaacetic acid (DTPA) was measured by sequential gastric scintigraphy 30 minutes after i.m. treatments. In other tests, GE was measured in 8 subjects after each i.m. treatment, followed 10 minutes later by 200 mg of erythromycin ethylsuccinate (ESS) suspension given orally. In a third group of tests, 7 subjects received an i.m. treatment, oral EES 10 minutes later, and were then brought to an advanced level of motion sickness short of vomiting. To induce motion sickness, blindfolded subjects made timed head movements while seated in a rotating chair. GE was measured immediately after rotation. GE half-life, rate constant, area under the curve (AUC), and lag time were calculated using conventional mathematical methods for analyzing exponential rate processes. GE parameters calculated for normal and motion-sick subjects given antimotion sickness drugs and EES were compared with those from subjects given i.m. treatments (control) only. In normal subjects, EES significantly (p < 0.05) increased the GE rate constant for all i.m. treatments and reduced the AUC for SAL, SCP, and PMZ by 49% (p < 0.05), 44% (p < 0.05), and 69% (p < 0.01), respectively. In motion-sick subjects, lag time was significantly (p < 0.05) increased, and the rate constant and AUC values were unchanged from control for all i.m. treatments. The authors conclude that oral EES reverses the gastrostatic actions of the antimotion sickness drugs but does not affect the inhibition of gastric emptying associated with motion sickness. The results suggest that motion sickness and antimotion sickness drugs reduce GE through different mechanisms.

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: a scintigraphic study.

Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.

[Comparison of the bioavailabilities of erythromycin estolate and erythromycin ethylsuccinate dry suspension preparations in steady state]. / Vergleich der Bioverfügbarkeiten von Erythromycinestolat bzw. Erythromycinethylsuccinat enthaltenden Trockensaft-Zubereitungen im steady state.

Relative bioavailability of erythromycin was determined after multiple-dose administration of erythromycin estolate in comparison to erythromycin ethylsuccinate both given as oral suspensions to twelve healthy volunteers. The daily erythromycin dose of erythromycin ethylsuccinate was 50% higher than the respective dose of erythromycin estolate; the dosage interval tau was 12 h for erythromycin estolate and 8 h for erythromycin ethylsuccinate. This scheme was planned in accordance to advices of the respective manufactures. Results of the study confirm the differences in extent of bioavailability of both erythromycin derivatives known from single-dose investigations. Furthermore, the experimental data show that a twice daily administration of 1000 mg erythromycin as erythromycin estolat resulted in sufficiently high plasma concentration of the active compound.

Influence of alcohol consumption on erythromycin ethylsuccinate kinetics.

The effect of ethyl alcohol ingestion on erythromycin kinetics was studied. Nine healthy volunteers, four males and five females, participated in the study. They received, in two separate occasions, 500 mg of erythromycin ethylsuccinate ester given with water or with an alcoholic beverage. The antibiotic was assayed in plasma, using a microbiological method. Absorption and disposition parameters were calculated according to classical pharmacokinetic techniques. A longer lag time and a decrease in AUC were observed when the antibiotic was given with alcohol. The differences were statistically significant. It is likely that the effect of alcohol on gastric emptying could be responsible for the delayed absorption of the antibiotic.