A sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of a new potent antihypertensive agent, TCV-116, and its two metabolites (M-I and M-II) in human serum or urine. After pre-treatment of the specimens, the analytes were determined using a column switching technique, except for the metabolites in urine which were determined by gradient elution mode HPLC. The quantitation limits for TCV-116, M-I and M-II were all 0.5 ng/ml in serum, and 0.5, 10 and 110 ng/ml in urine, respectively. The methods were applied to clinical trials of TCV-116.
"Some other combinations are also used and most work is done on plasma and urine samples. Techniques used are HPLC with fluorescence detector (Stenhoff et al., 1999; Gonzalez et al., 2002; Miyabayashi et al., 1996), LC-MS (Zhao et al., 1999), LC- UV (Qutab et al., 2007). All these methods are very tedious, time consuming and involve complex procedures, therefore require skilled individuals and expensive instruments. "
[Show abstract][Hide abstract] ABSTRACT: Candesartan-cilexetil, an angiotensin receptor blocker, exhibits low bioavailability after oral administration due to its low water solubility.
Chitosan is considered one of the most promising biopolymers for drug delivery as a vehicle and trimethyl chitosan is a water
soluble chitosan derivative. Trimethyl chitosan nanoparticles were prepared by the ionic crosslinking of a trimethyl chitosan
solution with tripolyphosphate, at ambient temperatures during stirring. SEM and TEM (scanning and transmission electron microscopy)
revealed trimethyl chitosan and trimethyl chitosan nanoparticles between 1,000–3,000 nm and 13–350 nm in size, respectively.
Candesartan-cilexetil was loaded on trimethyl chitosan nanoparticles, trimethyl chitosan, gum arabic and commercial water soluble chitosan using
an ultrasonic effect, and the potential of the polymers to increase the solubility of candesartan-cilexetil was investigated. Trimethyl chitosan nanoparticles are a superior vehicle for increasing the solubility of candesartan-cilexetil compared to trimethyl chitosan, gum arabic or commercial water soluble chitosan.
-chitosan nanoparticle-water solubility-bioavailability
Macromolecular Research 10/2010; 18(10):986-991. DOI:10.1007/s13233-010-1004-0 · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The influence of liver disease on the pharmacokinetics of candesartan, a long-acting selective AT1 subtype angiotensin II receptor antagonist was studied.
Twelve healthy subjects and 12 patients with mild to moderate liver impairment received a single oral dose of 12 mg of candesartan cilexetil on day 1 and once-daily doses of 12 mg on days 3-7. The drug was taken before breakfast. Serial blood samples were collected for 48 h after the first and last administration on days 1 and 7. Serum was analyzed for unchanged candesartan by HPLC with UV detection.
The pharmacokinetic parameters on days 1 and 7 revealed no statistically significant influence of liver impairment on the pharmacokinetics of candesartan. Following single dose administration on day 1, the mean Cmax was 95.2 ng.ml-1 in healthy subjects and 109 ng.ml-1 in the patients. The AUC0-infinity was 909 ng.h.ml-1 in healthy volunteers and 1107 ng.h.ml-1 in patients and the elimination half-life was 9.3 h in healthy volunteers and 12 h in the patients. At steady state on day 7, mean Cmax values were similar in both groups (112 vs 116 ng.ml-1); the AUC tau was 880 ng.h.ml-1 in healthy subjects and 1080 ng.h.ml-1 in patients while the elimination half-life was 10 h in healthy subjects and 12 h in the patients with liver impairment. The ACU0-infinity on day 1 was almost identical to the AUC tau on day 7. A moderate drug accumulation of 20%, which does not require a dose adjustment, was observed following once-daily dosing in both groups. No serious or severe adverse events were reported.
Mild to moderate liver impairment has no clinically relevant effect on candesartan pharmacokinetics, and no dose adjustment is required for such patients.
European Journal of Clinical Pharmacology 07/1998; 54(4):341-5. DOI:10.1007/s002280050471 · 2.97 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.