Administration, Inhalation ; Animals ; Disease Models, Animal ; Female ; Fluorine ; blood ; Fluorocarbons ; adverse effects ; pharmacokinetics ; Male ; Rabbits ; Rats

AIMTo develop a method for direct determination of perfluoropropane in canine whole blood and to study its pharmacokinetics after a suspension of perfluoropropane-containing albumin microcapsules was administered intravenously.

METHODSPerfluoropropane-containing albumin microcapsule suspension was administered intravenously to anesthetized canines at the dosage of 0.6 mL x kg(-1). Whole blood samples were collected and added directly into the purging glass tube in Tekmar 3000 Purge and Trap Concentrator coupled with a GC-MS for the determination of perfluoropropane. The pharmacokinetic parameters of perfluoropropane were calculated by non-compartment model statistics.

RESULTSThe linear range was 0.0168-4.03 mg x L(-1). The main pharmacokinetic parameters of perfluoropropane was obtained as follows: mean residence time (MRT) was (63 +/- 5) s, T1/2 was (44 +/- 4) s, Tmax was 30 s, Cmax was (2.20 +/- 0.20) mg x L(-1), AUC0-infinity was (96 +/- 11) mg x s x L(-1).

CONCLUSIONThe method is sensitive, specific and simple. It can be used to determine fluorocarbon contained in microcapsule ultrasound contrast agents for studying its pharmacokinetics.

Albumins ; Animals ; Area Under Curve ; Capsules ; Dogs ; Fluorocarbons ; administration & dosage ; blood ; pharmacokinetics ; Gas Chromatography-Mass Spectrometry ; methods ; Injections, Intravenous

OBJECTIVETo observe the effect of inhalation of aerosolized perfluorocarbon combined with tetramethylpyrazine on the hemodynamics and histopathology in a porcine model of acute lung injury.

METHODSNormal adult pigs were subjected to saline lavage of the bilateral lungs to induce acute lung injury and randomized subsequently into 3 groups for treatment with inhalation of perfluorocarbon, combined inhalation of perfluorocarbon and tetramethylpyrazine, or inhalation of tetramethylpyrazine. The changes of mean arterial pressure (MAP), PetCO(2), mPAP, CVP and PAWP were recorded at different time points following the lung injury, and the lung tissues were sampled for histological observations.

RESULTSThe MAP, mPAP, CVP and PAWP all increased significantly in the 3 groups after acute lung injury. Interventions with combined tetramethylpyrazine and perfluorocarbon inhalation significantly improved these indices as compared with inhalation of tetramethylpyrazine or perfluorocarbon alone (P<0.05). The pulmonary pathology was the mildest in the combined inhalation group, and the most severe in tetramethylpyrazine group.

CONCLUSIONCombined inhalation of perfluorocarbon and tetramethylpyrazine can effectively improve the oxygenation, reduce pulmonary arterial pressure?and ameliorate lung pathology in pigs with acute lung injury.

Acute Lung Injury ; drug therapy ; etiology ; pathology ; Administration, Inhalation ; Animals ; Drug Therapy, Combination ; Fluorocarbons ; administration & dosage ; Hemodynamics ; drug effects ; Lung ; pathology ; Phytotherapy ; Pyrazines ; administration & dosage ; Swine

The shortage of healthy blood resource and the problem of virus infection have urged the study of blood substitute. The technologies of modified hemoglobin, perfluorocarbons and Hb-vesicles have been developing quickly, and some of which have already been formed into large-scale preparation and production. However, there is no completed evaluation system for the blood substitute at present, and it is still hard to estimate the function of blood substitute completely. This article takes the evaluation of the blood substitute as a key point, discusses the evaluation parameters of blood substitute, and presents the physical and chemical property, the availability and safety as well as the preservation condition of the blood substitute. The data concerned are based on the studies in China and abroad and referred to the latest progress all over the world.
Animals ; Blood Substitutes ; administration & dosage ; standards ; Chemical Phenomena ; Erythrocytes ; drug effects ; metabolism ; Fluorocarbons ; administration & dosage ; adverse effects ; Hemoglobins ; administration & dosage ; adverse effects ; Humans ; Quality Control

AIMTo prepare bioadhesive microspheres of metronidazole (Metro) with prolonging resident time in the stomach and sustaining drug release.

METHODSThe microspheres were prepared by a drying-in-liquid method. The appearance, particle size and drug release in vitro were examined. The factors influencing bioadhesive property and drug release, such as ethyl cellulose (EC)/carbopol 934P (CP) ratio, particle size and Metro content were investigated.

RESULTSThe average diameter of the Metro-EC-CP microspheres was 559.9 microns. The release profiles of metronidazole were shown to fit to first-order equations well. With the increase of CP content in the Metro-EC-CP microspheres, the microspheres showed better mucoadhesion and faster drug release. The drug release rate decreased with the increase of particle size and the decrease of Metro content.

CONCLUSIONThe Metro-EC-CP microspheres have a sound mucoadhsive property and sustained drug release when the ratio of EC and CP was 17:3 and Metro content was 25%. The drug release was shown to last for 8 h in 0.1 mol.L-1 hydrochloric acid.

Acrylates ; Animals ; Anti-Infective Agents ; administration & dosage ; pharmacology ; Cell Adhesion ; Delayed-Action Preparations ; Female ; Fluorocarbons ; chemistry ; Gastric Mucosa ; physiology ; Metronidazole ; administration & dosage ; pharmacology ; Microspheres ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo develop a method for quantitative collection of exhaled gas in anesthetized dogs at given time following intravenous administration of octafluoropropane (OFP)-containing human albumin micropheres for assessing the gas kinetics of OFP.

METHODSOFP-containing albumin micropheres were administered intravenously at 0.4, 0.8 and 1.2 ml/kg, respectively, in anesthetized and ventilated dogs. The exhaled air samples were analyzed by gas chromatography-tandem mass spectrometry (GC-MS-MS).

RESULTSThe correlation curve between the area under curve (AUC) and administered dose was roughly linear (Y=1162.5X-417.38, r square=0.949 9). The total recovery rate was (119.49-/+27.62)% which was not significantly different from the rate of 100% (P>0.05). GC-MS-MS was accurate, sensitive, precise and applicable for OFP determination.

CONCLUSIONThe sampling method is useful for characterizing OFP pharmacokinetics in dogs, and also applicable for studying the pharmacokinetics of other gas-containing drugs.

Albumins ; administration & dosage ; analysis ; pharmacokinetics ; Animals ; Dogs ; Exhalation ; Female ; Fluorocarbons ; administration & dosage ; analysis ; pharmacokinetics ; Gas Chromatography-Mass Spectrometry ; methods ; Humans ; Injections, Intravenous ; Male ; Microspheres ; Reproducibility of Results

AIMTo investigate the preparation of pulsatile release tablets, the release of the drug in vitro and the pharmacokinetics in vivo.

METHODSDiltiazem hydrochloride (DIL) was used as model drug. The pulsatile release tablets were prepared by film-coated method using ethylcellulose and Eudragit L. The effect of formulation on pulsatile release of diltiazem hydrochloride was investigated under release rate test. The mechanism of pulsatile release of drug was proved by the test of water-uptake. The pharmacokinetic and bioavailability study in eight human subjects was performed by HPLC method.

RESULTSThe release of diltiazem hydrochloride effected by the formulation of the core tablets and the composition and thickness of the coating film. In vitro, the delayed-release time T10 was 4.4 h, the maximum release time Trm was 8.0 h and the pulsed-release time Trm-10 was 3.6 h. In vivo, the delayed-release time Tlag was 4.9 h, the peak time was 8.0 h and the pulsed-release time was 3.1 h. The relative bioavailability was 105%.

CONCLUSIONThe release of drug from pulsatile release tablets of diltiazem hydrochloride was shown to be in pulsed way both in vitro and in vivo.

Adult ; Antihypertensive Agents ; administration & dosage ; pharmacokinetics ; Biological Availability ; Chemistry, Pharmaceutical ; Delayed-Action Preparations ; Diltiazem ; administration & dosage ; pharmacokinetics ; Drug Delivery Systems ; Fluorocarbons ; chemistry ; Humans ; Male ; Polymethacrylic Acids ; chemistry

OBJECTIVETo prepare polyelectrolyte multilayer film-coated microbubble ultrasound contrast agent (UCA) and evaluate its effects in contrast imaging on normal rabbit's liver parenchyma.

METHODSPerfluorocarbon (PFC) -containing microbubble UCA (ST68-PFC) were prepared by sonication-based on surfactants (Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polylysine (PLL) and alginate (Alg) by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in contrast imaging on normal rabbit's liver parenchyma were assessed.

RESULTSThe obtained microbubble UCA exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film-coated UCA effectively enhanced the imaging of rabbit's liver parenchyma.

CONCLUSIONSThe novel microbubble UCA obtained via layer-by-layer self-assembly, when enabling more functions, has no obvious difference in enhancement effects compared with the premodified microbubbles. The polymers with chemically active groups (such as amino group and carboxyl group) can be used as the outermost layer for the attachment of targeting ligands to microbubbles, which allows the selective targeting of the microbubbles to desired sites.

Alginates ; chemistry ; Animals ; Contrast Media ; administration & dosage ; chemistry ; Fluorocarbons ; chemistry ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Liver ; diagnostic imaging ; Microbubbles ; Polylysine ; chemistry ; Rabbits ; Ultrasonography

We report two cases of surgical removal of a retained subfoveal perfluorocarbon liquid (PFCL) bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade. Two patients underwent pars plana vitrectomy with PFCL injection for rhegmatogenous retinal detachment. In both cases, a retained subfoveal PFCL bubble was noticed postoperatively by funduscopy and optical coherence tomography. Both patients underwent surgical removal of the subfoveal PFCL through a therapeutic macular hole and gas tamponade. The therapeutic macular holes were completely closed by gas tamponade and the procedure yielded a good visual outcome (best-corrected visual acuity of 20 / 40 in both cases). In one case, additional intravitreal PFCL injection onto the macula reduced the size of the therapeutic macular hole and preserved the retinal structures in the macula. Surgical removal of a retained subfoveal PFCL bubble through a therapeutic macular hole combined with intravitreal PFCL injection and gas tamponade provides an effective treatment option.
Aged ; Female ; Fluorocarbons/*administration & dosage ; Follow-Up Studies ; Fovea Centralis ; Humans ; Intravitreal Injections ; Retinal Perforations/diagnosis/physiopathology/*surgery ; Suction/*methods ; Tomography, Optical Coherence ; Visual Acuity ; Vitrectomy/*methods

We conducted a randomized animal study to determine whether there is a cumulative effect on hemodynamics, pulmonary function, and gas exchange when low dose nitric oxide (NO) is added to partial liquid ventilation (PLV) in acute lung injury. ighteen newborn piglets were saline-lavaged repeatedly, and randomly divided into two groups: PLV with perfluorocarbon group (n=8) and lavage only (control) group (n=10). Perfluorodecalin (30 mL/kg) was instilled into the endotracheal tube for 30 min, followed by 5-10 mL/kg/hr. Fifteen minutes after the completion of perfluorodecalin dosing, NO (10 ppm) was added to the inspiratory gas in an "on/off" manner. Perfluorodecalin instillation produced a significant improvement in gas exchange, pulmonary mechanics, shunt, and pulmonary arterial pressure (PAP). The addition of NO produced a further significant improvement in PaO2 and PAP. The "on/off" response to NO was seen apparently in PAP, PaO2, dynamic compliance, and shunt. All the variables in control group were remained at near the after-lavage levels without significant improvements until the end of the experiment. We concluded that NO might have a cumulative effect on gas exchange when combined with PLV, and this might be attributable to deceased PAP and V/Q mismatching.
Administration, Inhalation ; Animals ; Animals, Newborn ; Fluorocarbons/metabolism ; Hemodynamic Processes ; *Liquid Ventilation ; Nitric Oxide/administration & dosage/*metabolism ; Plasma Substitutes/metabolism ; Pulmonary Gas Exchange/*physiology ; Random Allocation ; *Respiratory Distress Syndrome, Adult ; Respiratory Mechanics ; *Respiratory Physiology ; Support, Non-U.S. Gov't ; Swine