Jan THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Table 1. Outline of administering doses, routes and sampling times *: 4 ml/hr/kg Bacillus subtilis
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1 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Jan. 1987
2 Jan THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Table 1. Outline of administering doses, routes and sampling times *: 4 ml/hr/kg Bacillus subtilis ATCC 6633
3 222(222) THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Jan Table 2. Pharmacokinetic parameters after intramuscular administration of HAPA -B and AMK in dogs *: One-compartment open model
4 Jan THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1
5 224(224) THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Jan, 1987 Fig. 2. Plasma concentrations after intramuscular administration of HAPA-B in dogs
6 Jan 1987 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-4 Fig. 3. Plasma concentrations after intravenous administration of HAPA-B in dogs
7 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Fig. 4. Plasma concentrations after drip intravenous administration of HAPA-B 6.25mg/kg in dogs Fig. 5. Plasma concentrations after drip intravenous administration of HAPA-B 25mg/kg in dogs
8 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Fig. 6. Plasma concentrations after drip intravenous administration of HAPA -B 100mg/kg in dogs Plate 1. TLC/Bioautogram of urine after intramuscular administration of HAPA -B25mg/kg in dogs TLC plate: Silica gel 60 (Merck) Solvent: CH3CN-CH3OH-CH3C00C2H5-28%NH4OH (4:2:1:5) Standard: HAPA-B (20, 10, 5, 2.5ƒÊg) Nos. 1-3: Dog urine collected 0-6 hours after administration Test organism: B. subtilis ATCC 6633 Medium: Nutrient agar (ph8.0)
9 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Table 4. Urinary excretion after intramuscular and intravenous administration of HAPA-B and AMK in dogs Table 5. Urinary excretion after drip intravenous administration of HAPA-B in dogs
10 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 Fig. 7. Plasma concentrations after administration of AMK 25mg/kg in dogs Fig. 8. Simulation curves of plasma concentration after drip intravenous administration of HAPA-B 6.25 mg/kg over various periods (Based on the results of intramuscular administration study) Time (hours)
11 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 1) NAGABHUSHAN, T.L.; A.B. COOPER, H. TSAI, P.J.L. DANIELS & G.H. MILLER : The syntheses and biological properties of 1-N-(S-4-amino-2-hydroxybutyry1)-gentamicin B and 1-N-(S-3-amino-2- hydroxypropiony1)-gentamicin B.J. Antibiotics 31: 681,
12 THE JAPANESE JOURNAL OF ANTIBIOTICS XL-1 STUDIES ON THE METABOLIC FATE OF ISEPAMICIN SULFATE (HAPA-B) IV. INTRAMUSCULAR, INTRAVENOUS AND DRIP INTRAVENOUS ADMINISTRATION OF HAPA-B IN DOGS KAZUNORI SERIZAWA, MARIYO SHIRAI, SATOKO ENDO, TADAKIYO SUZUKI and MASATAKA MORISHITA Pharmaceutical Research Laboratories, Toyo Jozo Co., Ltd. The plasma concentration and urinary excretion of isepamicin sulfate (HAPA-B) were studied following intramuscular, intravenous and drip intravenous administrations of 6.25, 25 and 100 mg/kg in dogs. Maximum plasma concentrations (Cmax) of HAPA-B after intramuscular, intravenous and drip intravenous administration depended on dosage levels. Biological half-lives (T1/2) and areas under plasma concentration-time curves (AUC) for the three different routes of administration were similar to each other. The peak plasma concentration of HAPA-B achieved with intramuscular administration was similar to that with a 1-hour drip intravenous administration at a dose level of 6.25 or 25 mg/kg. On the other hand, at a dose level of 100mg/kg, the Cmax following intramuscular administration was similar to that following 2-hour drip intravenous administration. It was, therefore, presumed that the plasma concentration curves which are similar to that of intramuscular administration can be obtained by regulating the infusion time. The observed Cm.x value for drip intravenous administration was a little higher than the theoretical Cm.x value for drip intravenous administration calculated from parameters for intramuscular administration. Simulation curves obtained for extended infusion times agreed more closely with observed curves than curves simulated for shorter infusion periods. These investigations showed that plasma concentration curves for any dosage levels can be estimated from parameters calculated from experimental data obtained using intramuscular or drip intravenous administration. HAPA-B was rapidly excreted into the urine after administration through any of these 3 routes and 71 `89% of the dose was excreted into the urine in 24 hours at all dosage levels. Bioautograms of thin-layer chromatographs of the 0 `6 hours urine after intramuscular administration showed single bands with a similar Rf value to that of the standard HAPA-B. No significant differences in plasma concentration and urinary excretion between HAPA-B and amikacin were observed upon intramuscular or intravenous administration of 25mg/kg.
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