Same-day single-dose vs large-volume split-dose regimens of polyethylene glycol for bowel preparation:A systematic review and meta-analysis

BACKGROUND Split-dose regimens(SpDs)of 4 L of polyethylene glycol(PEG)have been established as the“gold standard”for bowel preparation;however,its use is limited by the large volumes of fluids required and sleep disturbance associated with night doses.Meanwhile,the same-day single-dose regimens(SSDs)of PEG has been recommended as an alternative;however,its superiority compared to other regimens is a matter of debate.AIM To compare the efficacy and tolerability between SSDs and large-volume SpDs PEG for bowel preparation.METHODS We searched MEDLINE/PubMed,the Cochrane Library,RCA,EMBASE and Science Citation Index Expanded for randomized trials comparing(2 L/4 L)SSDs to large-volume(4 L/3 L)SpDs PEG-based regimens,regardless of adjuvant laxative use.The pooled analysis of relative risk ratio and mean difference was calculated for bowel cleanliness,sleep disturbance,willingness to repeat the procedure using the same preparation and adverse effects.A random effects model or fixed-effects model was chosen based on heterogeneity analysis among studies.RESULTS A total of 18 studies were included.There was no statistically significant difference of adequate bowel preparation(relative risk=0.97;95%CI:0.92-1.02)(14 trials),right colon Boston Bowel Preparation Scale(mean difference=0.00;95%CI:-0.04,0.03)(9 trials)and right colon Ottawa Bowel Preparation Scale(mean difference=0.04;95%CI:-0.27,0.34)(5 trials)between(2 L/4 L)SSDs and large-volume(4 L/3 L)SpDs,regardless of adjuvant laxative use.The pooled analysis favored the use of SSDs with less sleep disturbance(relative risk=0.52;95%CI:0.40,0.68)and lower incidence of abdominal pain(relative risk=0.75;95%CI:0.62,0.90).During subgroup analysis,patients that received low-volume(2 L)SSDs showed more willingness to repeat the procedure using the same preparation than SpDs(P<0.05).No significant difference in adverse effects,including nausea,vomiting and bloating,was found between the two arms(P>0.05).CONCLUSION Regardless of adjuvant laxative use,the(2 L/4 L)SSD PEG-based arm was considered equal or better than the large-volume(≥3 L)SpDs PEG regimen in terms of bowel cleanliness and tolerability.Patients that received low-volume(2 L)SSDs showed more willingness to repeat the procedure using the same preparation due to the low-volume fluid requirement and less sleep disturbance.

Pharmacokinetics,pharmacodynamics and safety of a single-dose long-acting Risperidone injection in Chinese patients with schizophrenia

In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.

Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

Development and validation of a rapid UPLC/MS method for the simultaneous determination of I3C, DIM, and related metabolites and its application to pharmacokinetics studies

Indole-3-carbinol(I3C) and diindolylmethane(DIM) are naturally derived dietary phytochemicals with promising anti-cancer properties that have been demonstrated both in vitro and in vivo. Using reversed-phase ultra-performance liquid chromatography(UPLC) coupled with mass spectrometry(MS), a rapid, specific, and high throughput method was developed and validated for the quantification and identification of I3 C, DIM, and other I3 C metabolites in plasma. Samples containing I3 C or DIM and the internal standard 4-methoxy indole(IS) were extracted using a liquid-liquid extraction technique. The mean recovery was 96.21% for I3 C and 108.5% for DIM. Separation was achieved using a Waters Acquity UPLC HSS T3, 1.8 μm, 2.1 mm×150 mm column and acetonitrile–water gradient elution. The flow rate was 0.3 m L/min and the run time was 9 min. The limits of detection and quantification for I3 C and DIM were 15 ng/m L and 25 ng/m L, respectively. Calibration curves for I3 C and DIM were linear(r2>0.99) over a concentration range of 0.025–20 μg/m L. Precision, accuracy, and stability analysis fulfilled the CDER guidelines criteria. The method was successfully applied to the determination of the pharmacokinetic parameters of I3 C or DIM after oral, intravenous, or intraperitoneal administration to Sprague Dawley rats. The method described here is superior over existing analytical methods for I3 C and its metabolites in terms of sensitivity, speed, and separation.