For infections in infants and children, the successful antibiotic treatment depends primarily on rapid diagnosis of the disease, identification of pathogenic microorganisms, and appropriate application of specialized pharmacokinetic and pharmacodynamic knowledge of antibiotics in children. In infants and children, the absorption, distribution, metabolism, and excretion of drugs may differ considerably in comparison with adults. Because of known toxicity, certain drugs such as chloramphenicol in high doses, the sulfonamides, and tetracycline should not be used in neonates. In this article, we describe these peculiarities of children and discuss the proper use of antibiotics in children.
Antibiotics/therapeutic use* ; Antibiotics/pharmacokinetics ; Antibiotics/metabolism ; Antibiotics/administration & dosage ; Child, Preschool ; Dose-Response Relationship, Drug ; Human ; Infant ; Pediatrics/methods* ; Time Factors

Pectin, a polysaccharide extracted from the cell wall of plants, was used as the drug carrier to synthesize the pectin-adriamycin conjugates (P(A)n). The structure of the conjugates was confirmed by UV and IR. The degree of esterification (DE) of the pectin was assessed, and it was found that DE significantly influenced the carboxy group contents, inherent viscosity and galacturonic acid contents of the pectin. The results of drug release test in vitro showed that the conjugate was stable in normal saline, but was gradually enzymolyzed to release the adriamycin in blood plasma and in lymph nodes. The results of lymphatic targeting study of P(A), demonstrated that the modification of DE or drug coupling capacity of pectin significantly influenced the lymphatic targeting characteristics of P (A)n. The adriamycin concentration of lymph nodes was 208 times higher than that of plasma after local injection of the P(A)n, of which the adriamycin content was 27.9% and the pectin was deesterificated 120 minutes by the use of hypothermy alkaline deesterification method.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; chemistry ; Esterification ; Lymph Nodes ; metabolism ; Pectins ; administration & dosage ; pharmacokinetics ; Rabbits

In this paper, we address the preparation of the EPC and HEPC sterically stabilized doxorubicin liposomes and report the data collected from further studies on pharmacokinetics in blood for choosing a better carrier in delivering the drugs. The pharmacokinetics of EPC and HEPC sterically stabilized liposomes (EPC-SSL, and HEPC-SSL) in Wistar rats were investigated by HPLC. The results showed that the mean residence time of HEPC-SSL in blood is 23.3 h, while that of EPC-SSL is 12.0 h. In conclusion, HEPC-SSL is a better carrier in delivering the drugs to the extravascular sites when compared with EPC-SSL.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; chemical synthesis ; pharmacokinetics ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; chemistry ; Hydrogenation ; Liposomes ; Phosphatidylcholines ; chemistry ; pharmacology ; Rats

OBJECTIVETo evaluate the adsorption and desorption of epirubicin (EADM) by carbon-coated iron nanocrystals (CCIN).

METHODSEADM standard curve was generated. After thorough mixture of CCIN and EADM with sonication, the mixture solution was centrifuged at high speed to obtain dissociated EADM for evaluating the adsorption capacity of CCIN. A dialyzer was used to evaluate the desorption of drug-loaded CCIN particles in different media (PBS, normal saline, or distilled water), at different temperatures, and with different quantities of loaded drug.

RESULTSThe adsorption of EADM by CCIN presented linear adsorption before saturation and saturation adsorption, with an adsorption saturation point of about 160 microg/mg. The desorption of EADM from CCIN particles was affected by such factors as the extraction media, temperature, and quantity of the loaded drug. Compared to distilled water, PBS and normal saline improved the release rate of EADM from the drug-loaded CCIN particles. Higher temperature also contributed to higher release rate of EADM. Higher release rate of EADM occurred after the CCIN particles adsorbed greater amount of EADM.

CONCLUSIONCCIN shows an EADM adsorption pattern of Langmuir isotherm adsorption. Such factors as higher temperature, PBS solution, higher speed of medium replacement, and more drug adsorbed all contribute to a higher release rate of EADM.

Adsorption ; Antibiotics, Antineoplastic ; chemistry ; pharmacokinetics ; Carbon ; chemistry ; Delayed-Action Preparations ; chemistry ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Epirubicin ; chemistry ; pharmacokinetics ; Iron ; chemistry ; Nanoparticles ; chemistry

AIMTo compare two methods, the total radioactivity assay (RA method) and the radioactivity assay after separation with high performance liquid chromatography (HPLC-RA method).

METHODS125I-Lidamycin was prepared by Iodogen method and separated by size exclusive high performance liquid chromatography. The pharmacokinetic parameters of lidamycin were assayed by two methods after intravenous injection to mice at the dose of 100 microg x kg(-1), and compared by statistical analysis.

RESULTSThe pharmacokinetic parameters (Vd, T1/2alpha, T1/2beta, K21, K10, K12, AUC and CL) showed significant difference between the two methods (P < 0.05).

CONCLUSIONThe HPLC-RA method was better than the RA method to determine unchanged 125I-lidamycin.

Aminoglycosides ; blood ; pharmacokinetics ; Animals ; Antibiotics, Antineoplastic ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Enediynes ; Female ; Iodine Radioisotopes ; Isotope Labeling ; Male ; Mice ; Sensitivity and Specificity

AIMTo study the pharmaceutical characterization and pharmacokinetics of long-circulating liposomes containing daunorubicin.

METHODSThe morphology of daunorubicin long-circulating liposome was surveyed under the transmission electron microscope. The size of daunorubicin long-circulating liposomes was determined by laser scatter method. The entrapment efficiency and accelerative experiment stability of the daunorubicin long-circulating liposomes were examined. Visible spectrophotometry and the HPLC method were established for determination of the daunorubicin in the long-circulating liposomes. The percent release of daunorubicin from long-circulating liposomes in HBS (pH 7.5) and rat serum at 37 degrees C were examined. The pharmacokinetics in rats were studied.

RESULTSThe high entrapment efficiency (> 85%) and stabilized long-circulating liposomes could be achieved. The drug was slowly released from the daunorubicin long-circulating liposomes. The drug released from liposomes was less than 10% in 24 h. The T1/2 alpha and AUC of long-circulating liposome were higher than those in injections.

CONCLUSIONThe long-circulating liposomes prepared by us have high encapsulation efficiency and the pharmaceutical characterization showed good stability, they can be used for clinical purpose.

Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Daunorubicin ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; Liposomes ; Male ; Phosphatidylethanolamines ; Polyethylene Glycols ; chemistry ; Random Allocation ; Rats ; Rats, Wistar

To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of epirubicin hydrochloride (EPI) in rat plasma, daunorubicin hydrochloride was used as internal standard. The plasma samples were deproteinated with methanol, and separation was performed on a reversed-phase CAPCELL PAK C18 column (3.0 mm x 50 mm, 3 microm). The mobile phase contained methanol-0.1% formic acid (80:20). Detection was carried out by multiple reaction monitoring on a HP1200-6410 QQQ LC/MS system. Different preparations of EPI solution, EPI-LIP (EPI-liposome) and EPI-LTSL (EPI-thermosensitive liposome) was administered in rats by i.v with the same dosage (12 mg kg(-1)). The pharmacokinetic model and parameters were fitted and calculated by the DAS ver2.0 software. The calibration curve was linear in the range of 0.01-50 microg mL(-1). The limit of quantification was 0.01 microg mL(-1). RSDs of intra- and interbatch precisions were all less than 11.9%. The average extract recovery was 89.3% and 92.1%, respectively. The pharmacokinetics of EPI in rats with all preparations were fitted to three compartments, which all fast distributed and slowly eliminated. The t1/2 alpha, t1/2 beta, t1/2 gamma, AUC(0-infinity), and MRT(0-infinity) of EPI-LTSL group were 7.5, 1.3, 12.6, 12.9, 3.7 times those of EPI solution group; and 1.6, 1.4, 12.3, 2.9, 2.6 times those of EPI-LIP group. Moreover, the CL of the latter two groups was about 13.4 times of the former EPI-LTSL group. EPI-LTSL can significantly improve AUC and prolong the circulation time of EPI in rat plasma.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Drug Carriers ; Epirubicin ; administration & dosage ; blood ; pharmacokinetics ; Liposomes ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry

OBJECTIVETo analyze the pharmacokinetics of intraperitoneal chemotherapy with mitomycin C (MMC) bound to activated carbon particles.

METHODSA nude mouse model with transplanted human gastric cancer was established. The mice were given MMC by i.v. or intraperitoneal (i.p.) injections, or given i.p. MMC bound to activated carbon particles (MMC-CH). Pharmacokinetic assays were carried out at different time points (0.5, 1, 2, 3, 6, 12 and 24 h) in 7 mice per each time point, to compare the MMC concentrations revealed by the above mentioned methods.

RESULTSThe MMC concentration in peritoneal exudate, omentum and lymph nodes of MMC-CH group was significantly higher than that of MMC solution i.p. group and MMC i.v. group (P < 0.001). On the other hand, the MMC level in serum was significantly lower than that in two control groups (P < 0.001). High MMC level was maintained longer than 24 hours in the MMC-CH group. Intraperitoneal chemotherapy with MMC solution resulted in a low MMC concentration in serum, peritoneal exudates and lymph nodes, and only a transient high level of MMC in the omentum. After i.v. administration, a significantly higher level of MMC concentration occurred in the serum, but only a shortly increased concentration of MMC in the omentum, and lower concentration in peritoneal exudate and lymph nodes as compared with those in the other two groups (P < 0.001).

CONCLUSIONHigh concentration of MMC in peritoneal exudate, omentum and lymph nodes maintained longer than 24 hours and a significantly lower MMC serum concentration can be achieved by administration of intraperitoneal administration of MMC bound to activated carbon particles.

Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Charcoal ; administration & dosage ; pharmacokinetics ; Female ; Humans ; Injections, Intraperitoneal ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mitomycin ; administration & dosage ; pharmacokinetics ; Neoplasm Transplantation ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology

OBJECTIVE: To observe the different tissue distributions of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after the injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice livers. METHODS: One hundred and eighty mice were randomly divided into 6 groups with 30 mice in each group: non-conjugated free ADM (Group 1); (22.3+/-6.2) nm in diameter ADM-PBCA-NP group (Group 2); (48.6+/-9.2) nm ADM-PBCA-NP group (Group 3); (101.9+/-20.3) nm ADM-PBCA-NP group (Group 4); (143.5+/-23.5) nm ADM-PBCA-NP group (Group 5), and (194.2+/-28.4) nm ADM-PBCA-NP group (Group 6). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours after the injection, respectively. The adriamycin concentrations in the collected livers, kidneys, spleens, hearts, lungs and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector. RESULTS: Compared with that of the control group, adriamycin was hardly detected in the heart muscles of the treatment groups (P<0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissues. The adriamycin concentrations of the mice liver and spleen in the experimental groups was significantly higher than those in the control group, except for the group with the nanoparticles diameters of (22.3+/-6.2) nm (P<0.05). The ADM-PBCA-NP in (101.9+/-20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in the liver was the group of (143.5+/-23.5) nm diameter (P<0.05). Adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3+/-6.2) nm diameter was not distributed in the tissues of the livers, kidneys, hearts, spleens, and lungs. CONCLUSION ADM-PBCA-NP with a 100 - 150 nm diameter range has the best liver targeting with slow medicine release. It also decreases the medicine distribution in the heart and other organs. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticle system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Enbucrilate ; administration & dosage ; pharmacokinetics ; Liver ; metabolism ; Male ; Mice ; Nanoparticles ; Particle Size ; Random Allocation ; Tissue Distribution

AIMTo evaluate the feasibility and accuracy of continuous monitoring of drug with a fiber optic chemical sensor (FOCS) in animal.

METHODSAn accurate optical design was used to enhance the intensity of light from a 100-micron optic fiber and the fluorescence signal could be detected. A new sol-gel method was used to fix the fluorescence substance 4-(N, N-dioctyl) amino-7-nitrobenz-2-oxa-1, 3-diazole (D-70) on the body fiber. The vary quenching means the vary of the concentration of adriamycin (ADM) in rabbit blood. ADM was determined by FOCS based on the fluorescence multiple quenching. In a simple animal model, the carotid artery was catheterized with a cannula, housing a 100-micron optic fiber.

RESULTSThe recovery of ADM was 99.4%-106.2%, the within-run and between-run RSDs were 6.6%-11.4% and 5.9%-11.7% respectively. The method permitted detection limits as low as 0.057 microgram.mL-1 at a signal-to-noise ratio of 3.

CONCLUSIONFiber-optic chemical sensor is potentially useful for monitoring blood drug in biomedical field.

Animals ; Antibiotics, Antineoplastic ; blood ; Area Under Curve ; Doxorubicin ; blood ; pharmacokinetics ; Drug Monitoring ; instrumentation ; methods ; Fiber Optic Technology ; methods ; Fluorescence ; Optical Fibers ; Rabbits ; Transducers