Hydrochlorothiazide pharmacokinetics

The changes in furosemide and hydrochlorothiazide pharmacokinetics appear to be of no practical importance, and the combination with an angiotensin II receptor antagonist can produce a significant and useful additional reduction in blood pressure. Details of these studies are given below. 

Williams RL, Davies RO, BermanRS, Holmes GI, Huber P, Gee WL,LinET,BenetLZ. Hydrochlorothiazide pharmacokinetics and pharmacologic effect the influence of indomethacin. JC/mPhamract)/ (1982) 22, 32-41. 

Other applications of the previously described optimization techniques are beginning to appear regularly in the pharmaceutical literature. A literature search in Chemical Abstracts on process optimization in pharmaceuticals yielded 17 articles in the 1990-1993 time-frame. An additional 18 articles were found between 1985 and 1990 for the same narrow subject. This simple literature search indicates a resurgence in the use of optimization techniques in the pharmaceutical industry. In addition, these same techniques have been applied not only to the physical properties of a tablet formulation, but also to the biological properties and the in-vivo performance of the product [30,31]. In addition to the usual tablet properties the authors studied the following pharmacokinetic parameters (a) time of the peak plasma concentration, (b) lag time, (c) absorption rate constant, and (d) elimination rate constant. The graphs in Fig. 15 show that for the drug hydrochlorothiazide, the time of the plasma peak and the absorption rate constant could, indeed, be... 

Some pharmacokinetic characteristics and the initial and usual maintenance dosages of hydrochlorothiazide are listed in Table 11-2. Although thiazide diuretics are more natriuretic at higher doses (up to 100-200 mg of hydrochlorothiazide), when used as a single agent, lower doses (25-50 mg) exert as much antihypertensive effect as do higher doses. In contrast to thiazides, the blood pressure response to loop diuretics continues to increase at doses many times greater than the usual therapeutic dose. 

Many other thiazides All basically similar to hydrochlorothiazide, differing only in pharmacokinetics ... 

Shoaf SE, Bramer SL, Bricmont P, Zimmer CA. Pharmacokinetic and pharmacodynamic interaction between tolvaptan, a non-peptide AVP antagonist, and fur-osemide or hydrochlorothiazide. J Cardiovasc Pharmacol 2007 50(2) 213-22. 

Huang XH, Qiu FR, Xie HT, Li J. 2005. Pharmacokinetic and pharmacodynamic interaction between irbesartan and hydrochlorothiazide in renal hypertensive dogs. J Cardiovasc Pharmacol 46 863-869. 

There are no published reports on the pharmacokinetics of the thiazide-type diuretics in horses. A bolus dose of a combination of dexamethasone (5 mg) and trichlormethiazide (200 mg), a product commonly used for treatment of udder edema in periparturient cattle, is occasionally used to treat edema in horses and there are anecdotal reports that it is efficacious. Hydrochlorothiazide (0.5- 0.7mg/kg orally twice daily) has also been used to enhance urinary potassium excretion and thereby limit the increase in serum potassium concentrations during an episode of hyperkalemic periodic paralysis in horses (Beech Lindborg 1996, Spier et al 1990 see Ch. 8). However, hydrochlorothiazide was less effective than acetazolamide (see below) and phenytoin in controlling the clinical signs, but it did limit the increase in the serum potassium ion concentrations during an oral potassium chloride challenge test (Beech Lindborg 1996). 

Example Hydrochlorothiazide (Hydro DIURIL, HCTZ) Route PO Pregnancy category D Pharmacokinetic Variably absorbed from GI tract excreted in urine. Not removed by hemodialysis. 

Pharmacokinetic studies of triamterene in combination with other drugs have also been done. In human subjects pharmacokinetics of triamterene with xipamide, 8 with hydrochlorothiazide,69 with propranolol and hydrochlorothiazide combination,70 and with oxprenolol and hydrochlorothiazide combination,71 have been studied. Pharmacokinetic and pharmacodynamic studies of the combination of furosemide retard and triamterene have been done in detail in healthy volunteers.72-75 In another study triamterene is reported to reduce the extrarenal elimination of digoxin, but induced no changes in digoxin-elicited inotropy.76... 

Abdelhameed, M.H. Chen, T.M. Chi W.L. Intrahepatic distribution of hydrochlorothiazide and quin-idine in rats Implications in ph macokinetics. J.Pharm.Sci., 1993, 82, 992-996 [whole blood plasma liver chlorothiazide (IS) rat pharmacokinetics]... 

Breithaupt-Grogler K, Ungethum W, Meurer-Witt B, Belz GG. Pharmacokinetic and (fynam-ic interactions of the angiotensin-converting en m e inhibitor imid rril with hydrochlorothiazide, bisoprolol and niivadipine. EurJ Clin Pharmacol (2001) 57,275-84. 

Nilsen OG, Sellevold OFH Romfo OS, Smedsrud A, Grynne B, Williams PEO, Klein-bloesem CH. Pharmacokinetics and effects on renal function following cilazapril and hydrochlorothiazide alone and in combination in healdiy subjects and hypertensive patients. BrJ Clin Pharmacol (1989) 27 (Suppl 2), 323S-328S. 

Weisser K, Schloos J, Jakob S, Muhlberg W, Platt D, MutscWer E. The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients. EurJ Clin Pharmacol... 

Symptomatic hypotension may occur when an angiotensin II receptor antagonist is started in patients taking high-dose diuretics. Potassium levels may be either increased, decreased or not affected. No clinically relevant pharmacokinetic interactions appear to occur between candesartan, eprosartan, irbesartan, losartan, telmisartan or valsartan and hydrochlorothiazide, although the bioavailability of hydrochlorothiazide may be modestly reduced. Similarly, there is no clinically significant pharmacokinetic interaction between valsartan and furosemide. 

In a randomised, crossover study in 13 healthy subjects, telmisartan 160 mg daily was given with hydrochlorothiazide 25 mg daily for 7 days. There was no difference in AUC and maximum plasma concentrations of either drug compared with when they were given alone. Similarly, no pharmacokinetic interactions were found between irbesartan and hydrochlorothiazide. ... 

Yoi C-L, Dias VC, Stai ier J. Multiple-dose pharmacokinetics of telmisartan and of hydrochlorothiazide foUowii concurrent administration in healthy subjects. J Clin Pharmacol (2000) 40,1323-30. 

Bianchetti G, PadovaniP, Coupez JM, GuinebaultP, HermannsP, Coupez-LopinotR, Guillet P, Thenot JP, Morselli PL. Pharmacokinetic interactions between hydrochlorothiazide, atenolol, and alfuzosin a new antihypertensive drug. Acta Pharmacol Toxicol (Copenh) (1986) 59 (Suppl 5), 197,... 

No pharmacokinetic interaction occurred between alfuzosin 5 mg and hydrochlorothiazide 25 mg in a single-dose study in 8 healthy subjects. The manufacturer notes that postural hypotension may occur in patients receiving antihypertensives when they start alfuzosin. ... 

Hydrochlorothiazide does not affect the pharmacokinetics or safety profile of valaciclovir. 

A study in a group of elderly subjects (65 to 83 years old) given valaciclovir 500 mg or 1 g three times daily for 8 days found that its safety profile was unchanged in the presence of hydrochlorothiazide, and was similar to that in young healthy subjects. The pharmacokinetics of the active metabolite of valaciclovir, aciclovir, were not significantly different. There would seem to be no reason for avoiding the concurrent use of either valaciclovir or aciclovir and hydrochlorothiazide. 

A study in 12 healthy subjects found that when sotalol 160 mg was given with hydrochlorothiazide 25 mg the pharmacokinetics of both drugs were unchanged. ... 

Sundquist H, Anttila M, Simon A, Reich JW. Comparative bioavailability and pharmacokinetics of sotalol adm blistered alone and in combination with hydrochlorothiazide. JCUn Pharmacol (1979) 19,557-64. 

No pharmacokinetic interaction appears to occur between hydrochlorothiazide and diltiazem or isradipine. Similarly, hydrochlorothiazide and triamterene did not alter nifedipine pharmacokinetics, and spironolactone does not alter felodipine pharmacokinetics. Combinations of diuretics and calcium-channel blockers are used clinically for their additive antihypertensive effects. 

The pharmacokinetics of isradipine and hydrochlorothiazide are not affected by concurrent use, and the pharmacokinetics of nifedipine are not affected by either hydrochlorothiazide or triamterene. Spironolactone 50 mg was found not to affect either the pharmacokinetics or the clinical effects of felodipine. ... 

Weir SJ, Dimmitt DC, Lanman RC, Morrill MB, Geising DH. Steady-state pharmacokinetics of diltiazem and hydrochlorothiazide administered alone and in combination. Biopharm Drug Dispos( 99S) 9,365-7. ... 

A study in 21 healthy subjects given diltiazem 60 mg 4 times daily (for 21 doses) and hydrochlorothiazide 25 mg twice daily (for 11 doses) either alone or in combination found that at steady-state there was no clinically significant pharmacokinetic interaction between the two drugs. ... 

In other studies indometacin had no effect on blood pressure in healthy subjects, no effect on the sodium excretion caused by hydrochlorothiazide, and did not affect the pharmacokinetics of hydrochlorothiazide. ... 

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