Bowel preparation is essential for successful colonoscopy examination, and the most important factor is the bowel preparation agent used. However, selection of a bowel preparation agent invariably involves compromise. Originally, bowel preparation was performed for radiologic and surgical purposes, when the process involved dietary limitations, cathartics, and enemas, which had many side effects. Development of polyethylene glycol (PEG) solution led to substantive advancement of bowel preparation; however, despite its effectiveness and safety, the large volume involved, and its salty taste and unpleasant odor reduce compliance. Accordingly, modified PEG solutions requiring consumption of lower volumes and sulfate-free solutions were developed. Aqueous sodium phosphate is more effective and better tolerated than PEG solutions; however, fatal complications have occurred due to water and electrolyte shifts. Therefore, aqueous sodium phosphate was withdrawn by the US Food and Drug Administration, and currently, only sodium phosphate tablets remain available. In addition, oral sulfate solution and sodium picosulfate/magnesium citrate are also available, and various studies have reported on adjunctive preparations, such as hyperosmolar or stimulant laxatives, antiemetics, and prokinetics, which are now in various stages of development.
Administration, Oral ; Cathartics/*administration & dosage ; Citrates/administration & dosage ; Citric Acid/administration & dosage ; Colonic Diseases/diagnosis ; Colonoscopy ; Humans ; Organometallic Compounds/administration & dosage ; Phosphates/administration & dosage ; Picolines/administration & dosage ; Polyethylene Glycols/administration & dosage

OBJECTIVETo evaluate the effectiveness and safety of different doses of caffeine in treatment of primary apnea in preterm infants.

METHODA total of 164 preterm infants (<32 weeks gestation), presented with primary apnea, were recruited in Tianjin Central Hospital of Gynecology and Obstetrics from October 2013 to December 2014. The patients were prospectively allocated into low-dose (loading 20 mg/kg and maintenance of 5 mg/(kg·d) after 24 h, n=82) and high-dose (loading 20 mg/kg and maintenance of 15 mg/(kg·d) after 24 h, n=82) groups of caffeine citrate treatment by using a random number table. The treatment effects, side effects of caffeine, and the clinical outcome of the preterm infants were compared between groups by χ(2) test or nonparametric test.

RESULTThe patients in low-dose group had birth weight of (1,237 ± 338) g, male gender of 43 (52%) and gestational age of (29.8 ± 3.4) weeks. The patients in high-dose group had birth weight of (1 262 ± 296) g, male gender of 45 (55%) and gestational age of (29.9 ± 2.7) weeks. The baseline characteristics including birth weight, gender and gestational age were comparable between the two groups. Frequency of apnea was significantly lower in high-dose group compared with low-dose group (10 (8, 15) vs.18 (13, 22), Z = -2.610, P = 0.009), and the success rate of removal of the ventilator was significantly higher in high-dose group compared with low-dose group (85% (70/82) vs.70% (57/82), χ(2) = 5.898, P = 0.015). The effective rate of caffeine treatment was significantly higher in high-dose group compared with low-dose group (82% (67/82) vs.61% (50/82), χ(2)=8.619, P = 0.003). No significant differences were observed concerning the incidence of caffeine-associated side effects including tachycardia, irritability, difficulty in feeding, hyperglycemia, hypertension, digestive disorders and electrolyte disturbances between two groups (P all > 0.05). There were no significant differences in the clinical outcomes of the preterm infants including death during hospitalization, chronic lung disease, other complications and duration of hospital stay between two groups (P all > 0.05).

CONCLUSIONA therapeutic regimen consisting of a loading dose of 20 mg/kg and maintenance dose of 15 mg/(kg·d) of caffeine citrate could improve the treatment effects and keep safety for primary apnea in preterm infants, and will not cause more adverse events.

Apnea ; drug therapy ; Birth Weight ; Caffeine ; administration & dosage ; Citrates ; administration & dosage ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; drug therapy ; Male ; Pregnancy ; Treatment Outcome

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.
Acute Kidney Injury/diagnosis/*drug therapy/*physiopathology ; Administration, Oral ; Animals ; Citrates/*administration & dosage ; *Dietary Supplements ; Kidney Failure, Chronic/*diet therapy/*physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Salt-Tolerance/*drug effects ; Treatment Outcome

The use of caffeine citrate for treatment of apnea in very low birth weight infants showed short-term and long-term benefits. A systematic review and meta-analysis of the literature was undertaken to document the effect providing caffeine early (0-2 days of life) compared to providing caffeine late (> or =3 days of life) in very low birth weight infants on several neonatal outcomes, including bronchopulmonary dysplasia (BPD). We searched MEDLINE, the EMBASE database, the Cochrane Library, and KoreaMed for this meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Jadad's scale. Studies were included if they examined the effect of the early use of caffeine compared with the late use of caffeine. Two reviewers screened the candidate articles and extracted the data from the full-text of all of the included studies. We included a total of 59,136 participants (range 58,997-59,136; variable in one study) from a total of 5 studies. The risk of death (odds ratio [OR], 0.902; 95% confidence interval [CI], 0.828 to 0.983; P=0.019), bronchopulmonary dysplasia (BPD) (OR, 0.507; 95% CI, 0.396 to 0.648; P<0.001), and BPD or death (OR, 0.526; 95% CI, 0.384 to 0.719; P<0.001) were lower in the early caffeine group. Early caffeine use was not associated with a risk of necrotizing enterocolitis (NEC) and NEC requiring surgery. This meta-analysis suggests that early caffeine use has beneficial effects on neonatal outcomes, including mortality and BPD, without increasing the risk of NEC.
Apnea/*drug therapy ; Bronchopulmonary Dysplasia/drug therapy ; Caffeine/*administration & dosage/adverse effects ; Citrates/*administration & dosage/adverse effects ; Enterocolitis, Necrotizing/etiology ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Very Low Birth Weight ; Risk Factors ; Treatment Outcome

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.
Administration, Cutaneous ; Aerosols ; Animals ; Azepines ; chemistry ; Calorimetry, Differential Scanning ; Cellulose ; analogs & derivatives ; chemistry ; Citrates ; chemistry ; Drug Delivery Systems ; Estradiol ; administration & dosage ; pharmacokinetics ; Plasticizers ; chemistry ; Polymers ; chemistry ; Skin Absorption ; Swine

BACKGROUND/AIMS: We investigated whether sodium picosulfate with magnesium citrate (SPMC) plus bisacodyl compares favorably with conventional polyethylene glycol (PEG) with respect to bowel cleansing adequacy, compliance, and safety. METHODS: We performed a multicenter, prospective, single-blinded study in outpatients undergoing daytime colonoscopies. Patients were randomized into a split preparation SPMC/bisacodyl group and a conventional split PEG group. We compared preparation adequacy using the Boston bowel preparation scale (BBPS), ease of use using a modified Likert scale (LS), compliance/satisfaction level using a visual analogue scale (VAS), and safety by monitoring adverse events during the colonoscopy between the two groups. RESULTS: A total of 365 patients were evaluated by intention to treat (ITT) analysis, and 319 were evaluated by per protocol (PP) population analysis (153 for SPMC/bisacodyl, 166 for PEG). The mean total BBPS score was not different between the two groups in both the ITT and PP analyses (p>0.05). The mean VAS score for satisfaction and LS score for the ease of use were higher in the SPMC/bisacodyl group (p<0.001). The adverse event rate was lower in the SPMC/bisacodyl group than in the PEG group (p<0.05). CONCLUSIONS: The SPMC/bisacodyl treatment was comparable to conventional PEG with respect to bowel preparation adequacy and superior with respect to compliance, satisfaction, and safety.
Adult ; Aged ; Cathartics/*administration & dosage ; Citrates/*administration & dosage ; Citric Acid/*administration & dosage ; Colon/*drug effects/surgery ; *Colonoscopy ; Drug Combinations ; Drug Therapy, Combination/methods ; Female ; Humans ; Intention to Treat Analysis ; Laxatives/*administration & dosage ; Male ; Middle Aged ; Organometallic Compounds/*administration & dosage ; Patient Compliance ; Patient Satisfaction ; Picolines/*administration & dosage ; Polyethylene Glycols/*administration & dosage ; Preoperative Care/methods/psychology ; Single-Blind Method ; Young Adult

The in situ gel systems can form gel in situ after administration to achieve sustained release, thus provides a promising strategy for drug delivery systems. The aim of this study was to design and prepare in situ gel systems for the oral delivery of ibuprofen (IBU-ISG) and study its pharmacokinetics in Beagle dogs. The characteristics of the basic material of gellan gum (Kelcogel, Kel) and sodium alginate (Manugel, M) were studied through investigating the complex viscosity of the Kel or M solution with or without different concentrations of calcium ion or sodium citrate to ascertain the amount range of the excipients. The measurement of complex viscosity of the solution (0. 5% Kel and 1% M) with different concentrations of sodium citrate and calcium ion was carried out to select the suitable proportion of calcium ion and sodium citrate. The formulation of binary IBU-ISG was optimized by monitoring the complex viscosity before gelling in vitro release property. The optimized formulation contains 1.0% sodium alginate, 0.5% gellan gum, 0. 21% sodium citrate and 0.056% calcium chloride. A single oral dose of IBU-ISG and reference formulation (IBU suspension) were given to each of the 6 healthy Beagle dogs, ibuprofen in plasma at different sampling times was determined by RP-HPLC. The pharmacokinetics parameters in 6 Beagle dogs were calculated. The Tmax of IBU-ISG and reference formulation were (1.8 +/- 0.6) and (0.4 +/- 0. 1) h. The Cmax values were (29.2 +/- 7.6) and (37.8 +/- 2.2) microg x mL(-1). The T(1/2) were (2.3 +/- 0.5) and (2.0 +/- 0.9) h, and the AUC(0-t) were (131.0 +/- 38.6) and (117.3 +/- 23.1) microg x mL(-1) x h, respectively. The binary IBU-ISG was successfully prepared.
Administration, Oral ; Alginates ; chemistry ; Analgesics, Non-Narcotic ; administration & dosage ; blood ; pharmacokinetics ; Animals ; Area Under Curve ; Calcium Chloride ; chemistry ; Citrates ; chemistry ; Delayed-Action Preparations ; Dogs ; Drug Compounding ; methods ; Drug Delivery Systems ; Excipients ; Female ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Ibuprofen ; administration & dosage ; blood ; pharmacokinetics ; Male ; Polysaccharides, Bacterial ; chemistry ; Viscosity