[Antihypertensive effect and pharmacokinetics of low molecular mass potassium alginate].
OBJECTIVE
To investigate the effect of low molecular weight potassium alginate (L-PA) on blood pressures in spontaneously hypertensive rats (SHRs) and its pharmacokinetics characteristics in mice.


METHODS
The systolic blood pressure (SBP) was measured by tail-cuff method in conscious SHRs. Forty rats were randomly assigned to the following five groups: control, hydrochlorothiazide (HCT, 6.25 mg/kg), L-PA in low, middle or high dose groups (100, 250, 500 mg/kg). SHRs were intragastrically (i. g.) administrated once daily for 28 days. The SBP was measured once weekly during drug treatment, and 3 and 6 days after drug with drawal. KM mice were i. g. administered with 100 mg/kg (74 MBq/kg) of 3H-L-PA. Ten microl blood samples were obtained from the tail vein at 2, 5, 10, 20, 30 min and 1, 2, 4, 6, 12, 24, 48, 72, 96, 120 or 144 h after drug administration for measuring radioactivities. Pharmacokinetics parameters of the oral administration of L-PA were analysed with DAS 2.0 software.


RESULTS
Twenty-one or 28 days after administration, the rats in the groups treated with HCT or L-PA at 100, 250 or 500 mg/kg had a significant decrease in SBP (P<0.01 vs control group). Three or 6 days after drug withdrawal, the antihypertensive effect of HCT disappeared (P>0.05), whereas the rats treated with 250 or 500 mg/kg L-PA still had lower SBP than the controls (P<0.01). The L-PA at a dose of 100 mg/kg also led to a significant decrease in SBP 3 days after drug withdrawal (P<0.05). The pharmacokinetics of L-PA (i. g.) was consistent with a two-compartment model, with 2.76 h of absorption half-life (t1/2, Ka), 42. 30 h of distributional half-life (t1/2alpha), 42. 31 h of elimination half-life (t1/2beta), and 36.28 h of terminal phase elimination half-life (t1/2z).


CONCLUSIONS
Oral administration of L-PA has significant anti-hypertensive effect, which can be maintained to 6 days after drug withdrawal. The sustaining anti-hypertensive effect of L-PA is probably associated with its slow elimination in vivo.
Ji
Wei
W
Department of Pharmacology & Biopharmaceutics, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Chen
Yu-Yun
YY
Du
Jun-Rong
JR
Yu
Dong-Ke
DK
Zheng
Xiao-Yuan
XY
Yang
Fang
F
Yu
Chuan-Xing
CX
Li
De-Shan
DS
Zhao
Chang-Yi
CY
Qiao
Kui-Yun
KY
D000464:Alginates / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D020723:Glucuronic Acid / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR
D000464:Alginates; D000959:Antihypertensive Agents; D006603:Hexuronic Acids; D020723:Glucuronic Acid