OBJECTIVESeizure is a common emergency in children with complicated pathogeny. Seizures are usually caused by complicated etiology and fever and febrile seizure are the commonest causes. Repeated and permanent seizures can damage the brain. So it is important to take active and effective measures to control seizure and high fever. Because most seizures and fever take place at home or out of hospital and it is difficult to administer drugs intravenously, it is important to explore an easy, safe, quick and effective way to control and prevent both seizure and fever. The present study aimed to explore the efficacy and safety of rectal administration of mixed ibuprofen and diazepam (IBU-DZP) solution.

METHODS(1) Animal study on the pharmacokinetics in rabbits and pharmacodynamics in rats after rectal administration with the mixed solution and on the irritability of the mixed solution to rectum. (2) Clinical study: Pharmacokinetics of the mixed solution in children after rectal administration were investigated.

RESULTS(1) Animal study: IBU and DZP were both rapidly absorbed from rectum with a peak blood level of (11.7 +/- 1.2) min and (9.4 +/- 2.7) min in rabbits, respectively. The mixed solution could effectively prevent the severity of seizures induced by pentetrazole and significantly suppressed fever induced by yeast. There were no remarkable pathological changes in rectal tissues after repeated rectal administration of the mixed solution. (2) Clinical study: IBU and DZP rapidly reached their peak blood levels at about 30 min and 15 min respectively after rectal administration to the children. The peak values were (57.8 +/- 7.9) mg/L and (450.1 +/- 158.7) microg/L, respectively. In fact, both of them reached levels that were much higher than their therapeutic levels in serum just at 5 min after administration, their blood levels were (41.4 +/- 5.5) mg/L and (321.8 +/- 53.9) microg/L, respectively.

CONCLUSIONSIBU-DZP mixed solution administered rectally is an easy, safe, quick and effective way to control and prevent both seizure and fever.

Administration, Rectal ; Animals ; Child ; Child, Preschool ; Diazepam ; administration & dosage ; pharmacokinetics ; Drug Therapy, Combination ; Humans ; Ibuprofen ; pharmacokinetics ; therapeutic use ; Infant ; Rabbits ; Rats ; Rats, Wistar ; Seizures, Febrile ; drug therapy

The pharmacokinetics of ibuprofen enantiomers were studied in rats after intravenous and oral administration of ibuprofen arginate by means of a chiral HPLC method. The pharmacokinetics of ibuprofen was stereoselective after intravenous and oral administration of ibuprofen arginate. The pharmacokinetic stereoselectivity was higher after oral administration than that after intravenous administration. The systematic (R)-(-)-to-(S)-(+) inversion might be more important than the presystematic one in the stereoselective pharmacokinetics after oral administration. Oral administration of ibuprofen arginate resulted in a very rapid absorption of (S)-(+)-ibuprofen (eutomer), and the absolute bioavailabilities of (S)-(+)-ibuprofen and (R)-(-)-ibuprofen were about 100% and 80%, respectively. Based on the systemic exposure of (S)-(+)-ibuprofen, it could be concluded that the pharmacological actions might be similar when ibuprofen arginate was given orally and intravenously, except some differences in the onset of action.
Absorption ; Administration, Intravenous ; Administration, Oral ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Arginine ; administration & dosage ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; Drug Combinations ; Ibuprofen ; administration & dosage ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Stereoisomerism

This study is to report the evaluation of the micromeritic properties of LubriTose AN, which is expected to provide preliminary theoretical basis for the direct compression technology. From the aspects of flowability, compressibility and dilution potential, the angle of repose, flow velocity, the Carr' index, tensile strength, elastic recovery, yield pressure and the lubricating ability of LubriTose AN were determined. Also, model drugs were selected to investigate the dilute potential under the desirable compressing performance. Compared to the physical mixtures, the flowability of LubriTose AN was better, and the deformation mechanism was the same with anhydrous lactose, both brittle deformation. The compressibility and compaction of LubriTose AN was slightly better than that of physical mixtures under low and moderate pressure. The dilution potential of LubriTose AN were high for most of hydrophobic drugs. The lubricate ability was desirable under different rotational speeds. LubriTose AN is an excellent co-processed excipient, which is helpful for the promotion and improvement of the tablet manufacturing level.
Drug Compounding ; Elasticity ; Excipients ; chemistry ; Glycerides ; chemistry ; Ibuprofen ; administration & dosage ; chemistry ; Lactose ; chemistry ; Lubricants ; chemistry ; Lubrication ; Particle Size ; Pressure ; Technology, Pharmaceutical ; methods ; Tensile Strength

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.
Calorimetry, Differential Scanning ; Carbon Dioxide ; chemistry ; Cellulose ; administration & dosage ; analogs & derivatives ; chemistry ; Crystallization ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; Ibuprofen ; administration & dosage ; chemistry ; Microscopy, Confocal ; Particle Size ; Povidone ; administration & dosage ; chemistry ; Solubility ; Spectrophotometry, Infrared ; Technology, Pharmaceutical ; methods

OBJECTIVEIntravenous indomethacin is the conventional treatment for patent ductus arteriosus (PDA) in preterm infants; however its use is associated with various side effects such as oliguria, gastrointestinal bleeding and reduction of cerebral perfusion. Intravenous ibuprofen has recently been used to treat PDA in preterm infants without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. Intravenous forms of indomethacin and ibuprofen are not available in Iran. This study aimed to examine and compare the efficacy and safety of oral ibuprofen and oral indomethacin for the treatment of PDA in preterm infants.

METHODSThirty-six infants (gestational age less than 34 weeks) who had echocardiographically confirmed PDA were enrolled in this study. The patients were randomly administered with three oral doses of either indomethacin (0.2 mg/kg, at an interval of 24 hrs) or ibuprofen (a first dose of 10 mg/kg, followed at an interval of 24 hrs by two doses of 5 mg/kg each) (n=18 each group). The rate of ductal closure, side effects, complications, and the infants' clinical course were recorded.

RESULTSThe ductus was closed in all of 18 patients (100%) in the ibuprofen group and in 15 (83.3%) patients in the indomethacin group (P > 0.05). There were no significant differences in the levels of serum blood urea nitrogen and creatinine between the two groups before and after treatment. Necrotizing enterocolitis (NEC) occurred in 3 patients in the indomethacin group and none in the ibuprofen group (P < 0.05). The survival rate at 1 month after treatment was 94% (17/18) in both groups. One infant in the ibuprofen group died from sepsis and one in the indomethacin group died as a result of NEC.

CONCLUSIONSOral ibuprofen is as effective as oral indomethacin for the treatment of PDA in preterm infants. Oral ibuprofen therapy is associated with a lower incidence of NEC.

Administration, Oral ; Ductus Arteriosus, Patent ; drug therapy ; Enterocolitis, Necrotizing ; epidemiology ; Humans ; Ibuprofen ; administration & dosage ; adverse effects ; therapeutic use ; Indomethacin ; administration & dosage ; adverse effects ; therapeutic use ; Infant, Newborn ; Infant, Premature

OBJECTIVETo study therapeutic effect and safety of early administration of oral ibuprofen in very low birth weight infants (VLBWIs) with patent ductus arteriosus (PDA).

METHODSA total of 64 symptomatic VLBWIs (within 24 hours after birth) with PDA confirmed by bedside Color Doppler ultrasound were randomly divided into two groups: treatment and control (n=32 each). The treatment group was orally administered ibuprofen within 24 hours after birth at 10 mg/kg, followed 24 hours later by a second dose of 5 mg/kg and 48 hours later by a third dose of 5 mg/kg. The control group was treated with placebo (normal saline) at 1 mL/kg, followed 24 hours later by a second dose of 0.5 mL/kg and 48 hours later by a third dose of 0.5 mL/kg. The therapeutic efficacies and adverse effects in both groups were observed.

RESULTSThe treatment group showed a significantly higher closure rate of ductus arterious than the control group after one course of treatment (84% vs 41%; P<0.01). The incidence rates of periventricular leukomalacia and bronchopulmonary dysplasia were significantly lower in the treatment group than in the control group (P<0.05). The duration of mechanical ventilation and mean hospitalization time were significantly shorter in the treatment group than in the control group (P<0.05). There were no significant differences in the incidence rates of intraventricular hemorrhage, early pulmonary hemorrhage and necrotizing enterocolitis between the two groups (P>0.05). No obvious adverse effects were observed in both groups.

CONCLUSIONSEarly administration of oral ibuprofen for treatment of PDA in VLBWIs can decrease the incidence rates of some early complications and shorten hospitalization time, but causes no significant adverse effects.

Administration, Oral ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; Ductus Arteriosus, Patent ; drug therapy ; Female ; Humans ; Ibuprofen ; administration & dosage ; adverse effects ; Infant, Newborn ; Infant, Very Low Birth Weight ; Length of Stay ; Male

The investigation was aimed to determine prognostic factors related to postherpetic neuralgia (PHN), and treatment options for preventing PHN. The data showed 34 (17.0%) out of 188 patients with herpes zoster had severe pain after 4 weeks, and 22 (11.7%) after 8 weeks, compared with 109 (58.0%) at presentation. The age (>or=50 yr), surface area involved (>or=9%), and duration of severe pain (>or=4 weeks) might be the main factors that lead to PHN. On the other hand, gender, dermatomal distribution, accompanied systemic conditions, and interval between initial pain and initiation of treatment might not be implicated in PHN. The subjects were orally received antiviral (valacyclovir), tricyclic antidepressant (amitriptyline), and analgesic (ibuprofen) as the standard treatment in the group 1. In addition to the standard medication, lidocaine solution was sub- and/or perilesionally injected in the group 2, while lidocaine plus prilocaine cream was topically applied to the skin lesions in the group 3. The rates of PHN in the 3 treatment groups were not significantly different, suggesting adjuvant anesthetics may not be helpful to reduce the severity of pain.
Acyclovir/administration & dosage/*analogs & derivatives ; Adolescent ; Adult ; Aged ; Amitriptyline/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Antidepressive Agents, Tricyclic/administration & dosage ; Antiviral Agents/administration & dosage ; Child ; Drug Therapy, Combination ; Female ; Herpes Zoster/*complications/drug therapy/physiopathology ; Humans ; Ibuprofen/administration & dosage ; Male ; Middle Aged ; Neuralgia/drug therapy/*etiology/physiopathology/prevention & control ; Prognosis ; Time Factors ; Valine/administration & dosage/*analogs & derivatives

The microstructures of ibuprofen-hydroxypropyl-bets-cyclodextrin (IBU-HP-beta-CyD) and ibuprofen-beta-cyclodextrin (IBU-beta-CyD) were observed by atomic force microscope (AFM). The high resolving capability of AFM has the tungsten filament probe with the spring constant of 0.06 N x m(-1). Samples were observed in a small scale scanning area of 10.5 nm x 10.5 nm and 800 x 800 pixels. The original scanning images were gained by tapping mode at room temperature. Their three-dimensional reconstruction of microstructure was performed by G3DR software. The outer diameters of HP-beta-CyD and beta-CyD are 1.53 nm. The benzene diameter of IBU is 0.62 nm, fitting to the inner diameters of HP-beta-CyD and beta-CyD. The benzene and hydrophobic chain of IBU enter into the hole of cyclodextrin at 1:1 ratio. The results were evidenced by IR, X-ray diffraction and the phase solubility.
2-Hydroxypropyl-beta-cyclodextrin ; Analgesics, Non-Narcotic ; administration & dosage ; chemistry ; Drug Delivery Systems ; Ibuprofen ; administration & dosage ; chemistry ; Microscopy, Atomic Force ; methods ; Spectrophotometry, Infrared ; X-Ray Diffraction ; beta-Cyclodextrins ; chemistry

Ductus Arteriosus ; surgery ; Ductus Arteriosus, Patent ; drug therapy ; therapy ; Humans ; Ibuprofen ; administration & dosage ; therapeutic use ; Indomethacin ; administration & dosage ; therapeutic use ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; drug therapy ; surgery ; therapy ; Ligation ; methods ; Treatment Outcome

The purpose of the present study is to use beta-cyclodextrin polymers (beta-CDP) with different cross-linked degree (CLD) to form inclusion complexes with ibuprofen and examine the effects of structural and compositional factors of beta-CDP on its drug loading and release behaviors. A series of beta-CDP with different CLD were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and 13C NMR spectrum. The beta-CDP was systemically characterized for the relation between the CLD of beta-CDP and the drug loading and release as well. The results of FT-IR and 13C NMR showed that similar peak-shaped vibration of beta-CDP and beta-CD implies that the polymer keeps the original characteristic structure of beta-CD. The CLD of the beta-CDP played a critical role in the drug loading and release, increasing the CLD resulted in reduction of drug loading, but increase in drug release.
Carbon Isotopes ; Cross-Linking Reagents ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Ibuprofen ; administration & dosage ; chemistry ; Magnetic Resonance Spectroscopy ; Pharmaceutical Preparations ; administration & dosage ; chemistry ; Polymers ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; beta-Cyclodextrins ; chemistry