The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/ kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 +/- 0.52 microgram/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination halflife were 0.173 +/- 0.033 h and 1.77 +/- 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 +/- 0.10 l/kg and 0.45 +/- 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 +/- 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.
Animals ; Anti-Bacterial Agents/*administration&dosage/blood/*pharmacokinetics/urine ; Area Under Curve ; *Buffaloes ; Cefotaxime/*administration&dosage/blood/*pharmacokinetics/urine ; Drug Administration Schedule ; Half-Life ; Male ; Tissue Distribution

The relative bioavailability of roxithromycin dispersive tablet in healthy volunteers was evaluated in this study. Its concentration in plasma was detected by high performance liquid chromatography (HPLC) after twenty healthy male volunteers were given each a single dose of 300 mg roxithromycin. The experiment data were obtained using DAS programme. The values of Cmax were 10.16+/-1.46 and 10.34+/-1.66 microg x ml(-1) at 2.33+/-0.61 and 2.28+/-0.62 h respectively; of t1/2 were 9.00+/-1.58 and 8.68+/-1.66 h respectively; of AUC0-->Tn were 143.32 +/-25. 80 and 138.93+/-22. 49 microg x h x ml(-1) respectively; of AUC0-->infinity were 158.63+/-26.86 and 153.77+/-24.75 microg x h x ml(-1) for test and reference drugs. Relative bioavailability of the tested roxithromycin was 103.63%+/-14.04%. The result showed that the two dispersive tablets are bioequivalent.
Administration, Oral ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; Humans ; Male ; Roxithromycin ; blood ; pharmacokinetics ; Tablets ; Therapeutic Equivalency ; Young Adult

The present study aimed to investigate the pharmacokinetic variation of ofloxacin based on gender-related difference in the expression of multidrug resistance-associated protein (Abcc2/Mrp2) in rat kidney. The concentrations of ofloxacin in rat plasma and urine were determined after tail vein administration (30 mg x kg(-1)) by high-performance liquid chromatography (HPLC) method. Expression of Mrp2 in kidney of male and female rats was qualitatively and quantitatively detected by immunohistochemistry and flow cytometry, separately. The results showed that AUC value of ofloxacin was lower in male rats than that in female rats and the total amount of ofloxacin excreted in the urine was higher in male rats than that in female rats. And the expression of Mrp2 in male rat kidney was higher than that in female rats. All results suggested that gender-related differences in pharmacokinetics of ofloxacin may be attributed to the differences in the expression of Mrp2 in kidney of male and female rats.
ATP-Binding Cassette Transporters ; metabolism ; Animals ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; urine ; Area Under Curve ; Female ; Kidney ; metabolism ; Male ; Ofloxacin ; blood ; pharmacokinetics ; urine ; Rats ; Rats, Wistar ; Sex Characteristics

OBJECTIVETo investigate the distribution of ornidazole in the salivary and serum of healthy adults and explore the feasibility of monitoring serum drug concentration with salivary.

METHODSSix volunteers received a single dose of 0.6 g ornidazole via intravenous infusion. The concentrations of ornidazole in the saliva and serum were assayed by high-performance liquid chomatography, and the correlation of the drug concentrations in saliva to that in serum was analyzed.

RESULTSThe concentration of ornidazole in the saliva was strongly associated with that in the serum (r = 0.825-0.969), and the ratio of saliva-to-serum concentration (S/P) of ornidazole was 0.99 ± 0.13.

CONCLUSIONDetection of saliva ornidazole concentration is feasible for monitoring the therapeutic concentration of ornidazole.

Adult ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Feasibility Studies ; Female ; Humans ; Male ; Ornidazole ; analysis ; blood ; pharmacokinetics ; Saliva ; metabolism ; Young Adult

It is very common to use Chinese medicine (CM) combined with Western medicine (WM) in clinical practice. The appropriate combination of CM with WM can reduce toxicity and enhance effects in order to make the best use of advantages and bypass the disadvantages. However, an inappropriate combination can not only affect the curative effect but even cause death. Therefore, strengthening the complementary advantages of the CM and WM to improve the therapeutic efficacy and reduce side effects has become an important research topic of clinical medicine and pharmacy. Many researchers try to clarify the effects of combining CM with WM on therapeutic efficacy and absorption, distribution, metabolism and excretion by pharmacodynamics and pharmacokinetics studies, providing evidence for clinical application. This review focuses on the new developments in the pharmacodynamics and pharmacokinetics of the combination of CM with WM in order to give references for clinical treatment.
Anti-Bacterial Agents ; pharmacology ; Blood Circulation ; drug effects ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; Humans ; Medicine, Chinese Traditional

The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t1/2alpha) and elimination half-life (t1/2beta) were 0.36 +/- 0.07 h and 7.42 +/- 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vdss) was 4.66 +/- 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (Cmax) was 0.43 +/- 0.06 microgram/ ml at 1.36 +/- 0.39 h (Tmax). The mean absorption (t1/2ka) and elimination half-life (t1/2beta) of NFLXGA were 0.78 +/- 0.27 h and 7.13 +/- 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 +/- 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.
Administration, Oral ; Animals ; Anti-Bacterial Agents/administration & dosage/blood/*pharmacokinetics ; Biological Availability ; Cross-Over Studies ; Glycine/administration & dosage/*analogs & derivatives/blood/pharmacokinetics ; Half-Life ; Injections, Intravenous/veterinary ; Male ; Norfloxacin/administration & dosage/*analogs & derivatives/blood/pharmacokinetics ; Swine/*metabolism ; Time Factors

The disposition kinetics of levofloxacin was investigated in six male crossbred calves following single intravenous administration, at a dose of 4 mg/kg body weight, into the jugular vein subsequent to a single intramuscular injection of paracetamol (50 mg/kg). At 1 min after the injection of levofloxacin, the concentration of levofloxacin in plasma was 17.2 +/- 0.36 microgram/ml, which rapidly declined to 6.39 +/- 0.16 microgram/ml at 10 min. The drug level above the MIC90 in plasma, was detected for up to 10 h. Levofloxacin was rapidly distributed from blood to the tissue compartment as evidenced by the high values of the distribution coefficient, alpha (17.3 +/- 1.65 /h) and the ratio of K12/K21 (1.83 +/- 0.12). The values of AUC and Vdarea were 12.7 +/- 0.12 microgram.h/ml and 0.63 +/- 0.01 l/kg. The high ratio of the AUC/MIC (126.9 +/- 1.18) obtained in this study indicated the excellent antibacterial activity of levofloxacin in calves. The elimination half-life, MRT and total body clearance were 1.38 +/- 0.01 h, 1.88 +/- 0.01 h and 0.32 +/- 0.003 l/kg/h, respectively. Based on the pharmacokinetic parameters, an appropriate intravenous dosage regimen for levofloxacin would be 5 mg/kg repeated at 24 h intervals when prescribed with paracetamol in calves.
Acetaminophen/administration & dosage/*pharmacokinetics ; Animals ; Anti-Bacterial Agents/administration & dosage/blood/*pharmacokinetics ; Area Under Curve ; Cattle/*metabolism ; Drug Therapy, Combination ; Half-Life ; Hybridization, Genetic ; Injections, Intravenous/veterinary ; Male ; Ofloxacin/administration & dosage/blood/*pharmacokinetics ; Time Factors

We developed a population pharmacokinetic model of vancomycin by integrating the effects of cystatin C and other demographic factors in a large population of Korean patients with normal serum creatinine concentrations to elucidate the precise role of serum cystatin C concentrations in the prediction of vancomycin clearance. A population pharmacokinetic model of vancomycin was developed using NONMEM software from a total of 1,373 vancomycin concentration measurements in 678 patients whose serum creatinine concentrations were lower than 1.2 mg/dL. Covariate selection revealed that cystatin C was the most influential factor and had negative influence (-0.78) in the relationship. Total body weight, sex, age, and serum creatinine were also significantly correlated with the clearance. The estimated intersubject variabilities of clearance and volume of distribution were 24.7% and 25.1%, respectively. A 14-fold difference in predicted trough concentrations was observed according to only cystatin C concentrations in a population of simulated individuals with median demographic characteristics. The use of serum cystatin C as marker of vancomycin clearance for more accurate predictions of serum vancomycin concentrations could be useful, particularly among patients with normal serum creatinine concentrations.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/blood/*pharmacokinetics ; Biological Markers/blood ; Body Weight ; Creatinine/*blood ; Cystatin C/*blood ; Demography ; Female ; Humans ; Male ; Middle Aged ; Models, Statistical ; Sex Factors ; *Software ; Vancomycin/blood/*pharmacokinetics ; Young Adult

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1degrees C. There was a significant reduction in the elimination halflife by 21.8% in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9%, the mean residence time by 19.9%, the area under the plasmaconcentration- time curve by 53.6% and the area under the moment curve by 62.3%. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits.
Animals ; Anti-Bacterial Agents/*administration&dosage/blood/*pharmacokinetics ; Area Under Curve ; Cephalosporins/*administration&dosage/blood/*pharmacokinetics ; Endotoxins/pharmacology ; Escherichia coli Infections/drug therapy/physiopathology ; Fever/chemically induced/*physiopathology ; Half-Life ; Injections, Intramuscular ; Male ; Rabbits

A study of amoxicillin pharmacokinetics was conducted in healthy goats and goats with chronic lead intoxication. The intoxicated goats had increased serum concentrations of liver enzymes (alanine aminotransferase and gamma-glutamyl transferase), blood urea nitrogen, and reactivated delta-aminolevulinic acid dehydratase compared to the controls. Following intravenous amoxicillin (10 mg/kg bw) in control and lead-intoxicated goats, elimination half-lives were 4.14 and 1.26 h, respectively. The volumes of distribution based on the terminal phase were 1.19 and 0.38 L/kg, respectively, and those at steady-state were 0.54 and 0.18 L/kg, respectively. After intramuscular (IM) amoxicillin (10 mg/kg bw) in lead-intoxicated goats and control animals, the absorption, distribution, and elimination of the drug were more rapid in lead-intoxicated goats than the controls. Peak serum concentrations of 21.89 and 12.19 microg/mL were achieved at 1 h and 2 h, respectively, in lead-intoxicated and control goats. Amoxicillin bioavailability in the lead-intoxicated goats decreased 20% compared to the controls. After amoxicillin, more of the drug was excreted in the urine from lead-intoxicated goats than the controls. Our results suggested that lead intoxication in goats increases the rate of amoxicillin absorption after IM administration and distribution and elimination. Thus, lead intoxication may impair the therapeutic effectiveness of amoxicillin.
Amoxicillin/blood/*pharmacokinetics/urine ; Animals ; Anti-Bacterial Agents/blood/*pharmacokinetics/urine ; Area Under Curve ; Chromatography, High Pressure Liquid/veterinary ; Goat Diseases/*chemically induced/metabolism ; Goats ; Half-Life ; Injections, Intramuscular/veterinary ; Injections, Intravenous/veterinary ; Lead Poisoning/etiology/metabolism/*veterinary ; Male