RESUMEN
One of the most promising approaches to design the optimal schedule for TDM provides a single determination of a drug content in the blood specimen being collected at the "ideal" sampling time equaled to the inverse value of the elimination rate constant. Three versions of the one-point method when the specimen was collected at the "ideal" time point (3 h after a single i.m. drug administration), as well as at the times of "maximum" (1 h after injection) and "minimum" (6 h after injection) concentrations were compared by the retrospective analysis of the routine TDM data obtained with HPLC-techniques in 47 patients treated with gentamicin or sisomicin. As optimal individualized doses were considered ones calculated on the base of three subsequent determinations of the aminoglycoside concentrations, i.e. 1, 3 and 6 h after injection, and the estimation of individual clearance values (Cli). The optimal doses (DCl) were calculated according to equation DCl = Dp.Cli/Clp, where Dp and Clp are population values of the dose (1 mg/kg) and Cl 72.4 ml/(h.kg), respectively. The approximate values of the individual doses (D) were calculated according to equation D = Dp.Cp/Ci, where Ci is the individual drug serum concentration 1, 3 or 6 h after administration and Cp is the corresponded population value (4.8, 1.9 and 0.8 mg/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Monitoreo de Drogas/métodos , Gentamicinas/administración & dosificación , Enfermedades Pulmonares/tratamiento farmacológico , Sisomicina/administración & dosificación , Disponibilidad Biológica , Gentamicinas/sangre , Gentamicinas/farmacocinética , Humanos , Enfermedades Pulmonares/metabolismo , Sisomicina/sangre , Sisomicina/farmacocinética , Factores de TiempoRESUMEN
Clinical efficacy of rifampicin, a semisynthetic broad spectrum antibiotic was estimated in 247 patients with purulent inflammations. It was shown advisable to use rifampicin intravenously in treatment of severe bronchopulmonary pathology, disorders of the bile excretion system, osteomyelitis, severe wound infections and in prophylaxis of postoperative purulent complications in cardiovascular surgery and other cases. High rifampicin sensitivity of staphylococci and streptococci belonging to various species was revealed. Rifampicin was found to be less active against gramnegative pathogens. The isolation frequency of rifampicin sensitive strains of E. coli, Proteus spp., Klebsiella spp. and P. aeruginosa amounted to 88.4, 52.1, 58.8 and 49.3 per cent respectively.
Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Rifampin/uso terapéutico , Bacterias/efectos de los fármacos , Infecciones Bacterianas/microbiología , Colangitis/tratamiento farmacológico , Colangitis/microbiología , Farmacorresistencia Microbiana , Hepatitis/tratamiento farmacológico , Hepatitis/microbiología , Humanos , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiologíaRESUMEN
The influence of hemosorption and hemodialysis on the pharmacokinetics of cefazolin was studied in 20 patients with chronic and acute renal insufficiency. The integral mean value of the antibiotic extraction coefficient in hemosorption was approximately 2 times higher than that in hemodialysis. In the first case the value of this parameter systematically lowered with time (the constant of the process rate amounted to 0.89 h-1), while in the second case it was constant.
Asunto(s)
Cefazolina/sangre , Hemoperfusión , Diálisis Renal , Cefazolina/uso terapéutico , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Cinética , Factores de TiempoRESUMEN
Pharmacokinetics of rifampicin on its single intravenous and oral administration to rats in doses of 25 and 50 mg/kg and on its intravenous administration to dogs in doses of 8 and 25 mg/kg was studied. When the antibiotic was administered intravenously to the animals, its pharmacokinetics was nonlinear. The linearity distortion in the rats was lower than in the dogs. However, the pharmacokinetic data relevant to the antibiotic administration in the above doses were satisfactorily described by the biexponential equation. The absolute extent of rifampicin systemic absorption following oral administration to the rats was 60 to 85 per cent. Tissue availability of the antibiotic on its intravenous administration was lower than that on its oral administration.
Asunto(s)
Rifampin/metabolismo , Absorción , Administración Oral , Animales , Perros , Relación Dosis-Respuesta a Droga , Inyecciones Intravenosas , Cinética , Ratas , Ratas Endogámicas , Rifampin/administración & dosificación , Factores de Tiempo , Distribución TisularRESUMEN
The effect of hemosorption and hemodialysis on the pharmacokinetics of sisomicin was studied in 17 patients with acute and chronic renal insufficiency. The value of the antibiotic extraction coefficient in hemosorption was almost 2 times higher than that in hemodialysis. In patients on hemosorption, extracorporeal elimination of the antibiotic was of the saturation nature. It was characterized by systematic diminishing of the extraction coefficient, while in patients on hemodialysis, it did not depend on the time (the value of the extraction coefficient was constant). In this connection it is recommended that the rate of diminishing of the extraction coefficient in hemosorption be estimated. Since sisomicin is rapidly absorbed by the column it is not advisable to administer sisomicin to patients before hemosorption.
Asunto(s)
Lesión Renal Aguda/terapia , Hemoperfusión , Fallo Renal Crónico/terapia , Diálisis Renal , Sisomicina/metabolismo , Lesión Renal Aguda/metabolismo , Humanos , Fallo Renal Crónico/metabolismo , Factores de TiempoRESUMEN
The pharmacokinetics of sisomicin and gentamicin in the cortical and medullary layers of the kidneys was studied on rats. The antibiotics were administered daily in doses of 12.5 and 25 mg/kg a day. The levels of the antibiotics in the cortical layer were much higher than those in the medullary layer. The use of a twice as higher dose in the first case resulted in a less than a two-fold increase in the drug concentration, while in the second case the increase was more than two-fold. Prognosis of the pharmacokinetics of aminoglycosides used for 8-16 days was achieved with the help of the constants of the two-compartmental model. It was shown that the actual levels of sisomicin and gentamicin in the kidney medullary layer did not significantly differ from the estimated ones and the levels of the drugs in the cortical layer were much lower than the predicted ones. The distorted linearity of the aminoglycoside pharmacokinetics must be mainly due to saturation of the cortical layer with the drugs.
Asunto(s)
Gentamicinas/metabolismo , Corteza Renal/metabolismo , Médula Renal/metabolismo , Sisomicina/metabolismo , Animales , Gentamicinas/administración & dosificación , Cinética , Ratas , Ratas Endogámicas , Sisomicina/administración & dosificaciónRESUMEN
The pharmacokinetics of sisomicin administered intramuscularly to rats in daily doses of 12.5 and 25 mg/kg for 30 days was studied. After a single administration of the drug in the above doses the highest and the lowest levels of sisomicin were observed in the kidney cortical layer and liver, respectively. The antibiotic level in the tissues rose with an increase in the antibiotic dose and duration of the drug use. The two-fold rise in the dose resulted in an elevation in the sisomicin level in the kidney cortical layer by 1.7 times, in the medullary layer by 3 times, and in the blood serum, lungs and spleen by 2.3, 1.2 and 1.5 times, respectively. After treatment with a dose of 25 mg/kg for 8 days the antibiotic level in all tissues studied was higher than that after the first administration of the drug: in the cortical and medullary layers of the kidneys by 5-7 times and in the blood serum and other tissues by 1.2-2 times. When sisomicin was used repeatedly in any dose, stabilization of or some decrease in the mean integral concentration of the antibiotic in the kidney cortical layer and a continuous increase of this value with respect to the medullary layer (up to the 30th day) were noted. The difference between the antibiotic levels in the kidney layers after the repeated administration of the drug was less pronounced than that after a single administration of the drug. The cumulation index of sisomicin in the kidney cortical layer persisted at the same level and that in the medullary layer gradually increased. In this connection it is concluded that correlation between the sisomicin nephrotoxic effect and the level of the antibiotic in the kidney cortical layer is more pronounced than that in the medullary layer.
Asunto(s)
Gentamicinas/metabolismo , Sisomicina/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Intramusculares , Corteza Renal/metabolismo , Médula Renal , Cinética , Ratas , Ratas Endogámicas , Sisomicina/administración & dosificación , Factores de Tiempo , Distribución TisularRESUMEN
A modification of the microbiological agar-diffusion method for rapid determination of gentamicin, sisomycin and kanamycin levels in the blood serum of patients is described. The decrease in the time for determination of the antibiotic levels in the serum specimens with the modified method was provided by the use of a higher inoculation dose of the test microbe, higher levels of the incubation temperature and an enriched nutrient medium. The assay time was decreased from 18 to 3--4 hours as compared to the routine agar-diffusion method.
Asunto(s)
Bioensayo/métodos , Gentamicinas/sangre , Kanamicina/sangre , Sisomicina/sangre , Bacillus subtilis/efectos de los fármacos , Medios de Cultivo , Humanos , Esporas Bacterianas/efectos de los fármacos , Temperatura , Factores de TiempoRESUMEN
During the 96-day flight aboard the Salyut-6 station the crewmembers showed a satisfactory response to bicycle ergometry of moderate load. However, cardiovascular regulation during exercise declined, particularly by the end of the first and the beginning of the second month. This was mainly associated with deconditioning due to an inadequate work load. Its increase helped to restore an initial level of circulation during exercise by the end of the mission.
Asunto(s)
Circulación Sanguínea , Esfuerzo Físico , Vuelo Espacial , Presión Sanguínea , Humanos , Cinetocardiografía , Masculino , Pulso Arterial , Factores de Tiempo , U.R.S.S. , IngravidezRESUMEN
The kinetics of urine nitrogen in the blood serum and morphological changes in the kidneys after a single and repeated intramuscular administrations of the antibiotic in doses of 12.5 and 25 mg/kg a day were studied in Wistar rats. When sisomycin was administered in a dose of 12.5 mg/kg, the increase in the urine nitrogen level after 1--30 injections was reversible, whereas at a dose of 25 mg/kg it became irreversible already after the 5th injection. Maximum deviations in the urine nitrogen level observed within 3--6 hours after each injection of sisomicin were recorded after the 5th injection of the drug in a dose of 12.5 mg/kg and even after the 1st injection of the drug in a dose of 25 mg/kg. The deviations increased up to the 5th and 16th injection of sisomycin in doses of 12.5 and 25 mg/kg respectively. Later the deviations were less pronounced. Regardless of the dose, adipose degeneration in renal tubules was registered after 8--16 injections of the drug. By the 30th and 16th days of the drug administration in doses of 12.5 and 25 mg/kg respectively, the above changes also decreased. On the whole, pronounced functional and morphological changes in the kidneys correlated with the antibiotic dose. Relationship between the time from the beginning of sisomycin administration and the moment when the average integral concentration of the urine nitrogen increased to the upper limit of normal and the logarithm of the average integral concentration of the antibiotic in the serum was found. The safety of the clinical schemes for the use of sisomicin was estimated with the help of this relationship with respect to its nephrotoxic effect.
Asunto(s)
Gentamicinas/toxicidad , Riñón/efectos de los fármacos , Sisomicina/toxicidad , Animales , Nitrógeno de la Urea Sanguínea , Relación Dosis-Respuesta a Droga , Riñón/patología , Cinética , Ratas , Sisomicina/sangre , Factores de TiempoRESUMEN
The pharmacokinetics of sisomicin was studied on Wistar rats. The antibiotic was used in single or repeated doses of 12.5 and 25 mg/kg. The kinetic data of the antibiotic titration in blood serum within 1 and 24 hours of intramuscular administration of the drug were formalized with the use of a linear two-compartment model. The average values of the elimination constant and the constants of sisomycin transfer from the central compartment into the peripheral one were 0.64, 0.34 and 0.13 hours-1 respectively. The value of the apparent distribution volume in the central compartment was 0.38 ml/kg and that of the stationary and kinetic distribution volumes was 1.37 and 3.06 1/kg respectively. The value of the general clearance was 0.24 1/(kg.hour) and that of the sisomicin half-life was 8.7 hours. Comparison of the antibiotic levels estimated with a model and actually measured in the blood after repeated administrations revealed the drug cumulation. When the antibiotic was used in a dose of 25 mg/kg daily, its cumulation was observed earlier (by the 5th--8th day) than on its use in a dose of 12.5 mg/kg (by the 30th day). Irrespective of the dose, sisomicin cumulation was accompanied by prolongation of the antibiotic half-life in the rats.
Asunto(s)
Gentamicinas/toxicidad , Riñón/efectos de los fármacos , Sisomicina/toxicidad , Animales , Femenino , Cinética , Masculino , Matemática , Ratas , Sisomicina/administración & dosificación , Sisomicina/sangre , Factores de TiempoRESUMEN
The effect of Actinomyces rimosus RNAase on the variolovaccine virus was studied. The inhibitory effect of the Actinomyces rimosus RNAase on the variolovaccine virus reproduction in the tissue culture cells was shown. In the experiments with the use of chick embryons and rabbits this effect was less pronounced. A 10 time increase in the infection multiplicity both in the tissue culture and the chick embryons had no noticeable effect on the level of the virus inhibition. It was supposed that the inhibitory effect of the RNAase on the variolovaccine was associated with impairment of the cell metabolism.