Online Pharmacy, Tramadol, Paxil, antibiotics, amoxicillin, zithromax, Rx Online, pharmaceuticals, DHEA, prescription medications, prescription drugs.

Drugs online research references

J Control Release. 2003 Jan 17;86(2-3):279-92.
Prodrugs of purine and pyrimidine analogues for the intestinal di/tri-peptide transporter PepT1: affinity for hPepT1 in Caco-2 cells, drug release in aqueous media and in vitro metabolism.

Thomsen AE, Friedrichsen GM, Sorensen AH, Andersen R, Nielsen CU, Brodin B, Begtrup M, Frokjaer S, Steffansen B.

Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

A general drug delivery approach for increasing oral bioavailability of purine and pyrimidine analogues such as acyclovir may be to link these compounds reversibly to stabilized dipeptide pro-moieties with affinity for the human intestinal di/tri-peptide transporter, hPepT1. In the present study, novel L-Glu-Sar and D-Glu-Ala ester prodrugs of acyclovir and 1-(2-hydroxyethyl)-linked thymine were synthesized and their affinities for hPepT1 in Caco-2 cells were determined. Furthermore, the degradation of the prodrugs was investigated in various aqueous and biological media and compared to the corresponding hydrolysis of the prodrug valaciclovir. Affinity studies showed that the L-Glu-Sar prodrugs had high affinity for hPepT1 (K(i) approximately 0.2-0.3 mM), whereas the D-Glu-Ala prodrugs had poor affinity (K(i) approximately 50 mM). The pH-rate profiles of the prodrugs D-Glu[1-(2-hydroxyethyl)thymine]-Ala and L-Glu[acyclovir]-Sar showed specific base catalyzed degradation at pH above 4.5 and 5.5, respectively. This implicates that the degradation rates at pH approximately 7.4 (t(1/2) approximately 3.5 and 5.5 h) are approximately 25 times faster than at upper small intestinal pH approximately 6.0. In 10% porcine intestinal homogenate and 80% human plasma the half-lives of the L-Glu-Sar prodrugs were approximately between 45 and 90 min indicating a limited enzyme catalyzed degradation. In contrast, valaciclovir underwent extensive enzyme catalyzed hydrolysis in 10% porcine intestinal homogenate (t(1/2) approximately 1 min). In conclusion, L-Glu-Sar may potentially function as pro-moiety for purine and pyrimidine analogues, where release of parent compound primarily is controlled by a specific base catalyzed hydrolysis. Acyclovir is quantitatively released at the relevant pH 7.4, whereas the 1-(2-hydroxyethyl)-linked thymine is released instead of the parent compound thymine.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12526824&dopt=Abstract

liv.ac.uk

This paper retrospectively reviews features of postherpetic neuralgia (PHN) in up to 279 personal patients in relation to treatment outcome when treated with tricyclic antidepressants (TCAs). Factors affecting characteristics of PHN: (i) Patients with allodynia (89%) and/or burning pain (56%) have a much higher visual analogue pain intensity score than those without; (ii) Acyclovir (ACV) given for acute shingles (HZ) does not reduce the incidence of subsequent PHN, but reduces the pain intensity in PHN patients with allodynia; (iii) ACV given for acute HZ reduces the incidence of burning pain in subsequent PHN, but not of allodynia; (iv) ACV given for acute HZ reduces the incidence of clinically detectable sensory deficit in subsequent PHN. Factors affecting outcome of TCA-treated PHN: (i) The point in time at which TCA treatment is commenced is by far the most critical factor: started between 3 and 12 months after acute HZ onset, more than two-thirds obtain pain relief (NNT=1.8); between 13 and 24 months, two-fifths (41%) (NNT=3.6); and more than two years, one-third (NNT=8.3). Background and paroxysmal pain disappear earlier and are more susceptible of relief than allodynia. (ii) Twice as many (86%) of PHN patients without allodynia obtain pain relief with TCA treatment than those with (42%); (iii) the use of ACV for acute HZ more than halves the time-to-relief of PHN patients by TCAs; (iv) PHN patients with burning pain are significantly less likely to obtain pain relief with TCAs than those without (p<0.0001).

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12527312&dopt=Abstract

J Pharmacol Exp Ther. 2003 Feb;304(2):781-91.
Interactions of the dipeptide ester prodrugs of acyclovir with the intestinal oligopeptide transporter: competitive inhibition of glycylsarcosine transport in human intestinal cell line-Caco-2.

Anand BS, Patel J, Mitra AK.

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110-2499, USA.

The oligopeptide transporter may be exploited to enhance the absorption of drugs by synthesizing their dipeptide ester prodrugs, which may be recognized as its substrates. Various dipeptide esters of acyclovir (ACV), an antiviral nucleoside analog, were synthesized. Enzymatic hydrolysis and affinity of the prodrugs toward the human intestinal peptide transporter hPEPT1 were studied using the human intestinal Caco-2 cell line. Affinity studies were performed by inhibiting the uptake of [(3)H]glycylsarcosine by the prodrugs. The uptake of glycylsarcosine was found to be saturable at higher concentrations and was competitively inhibited by the prodrugs of ACV. All prodrugs except Tyr-Gly-ACV demonstrated a higher affinity (1.41-4.96 mM) toward hPEPT1 than cephalexin (8.19 +/- 2.12 mM), which was used as a positive control. Two prodrugs, Gly-Val-ACV and Val-Val-ACV, showed comparable affinity to Val-ACV, an amino acid prodrug of ACV recognized by PEPT1/PEPT2. The permeability of Gly-Val-ACV (2.99 +/- 0.59 x 10(-6) cm/s) across Caco-2 was comparable with that of Val-ACV (3.01 +/- 0.21 x 10(-6) cm/s) and was significantly inhibited (63%) in presence of glycylsarcosine. The transport of GVACV across Caco-2 was saturable at higher concentrations, and the parameters were calculated as K(m) 3.16 +/- 0.31 mM and V(max) 0.014 +/- 0.00058 nmol cm(-2) min(-1). Overall, the results suggest that the dipeptide prodrugs of ACV have a high affinity toward the intestinal oligopeptide transporter hPEPT1 and therefore seem to be promising candidates in the treatment of ocular and oral herpesvirus infections, because cornea and intestinal epithelia seem to express the oligopeptide transporters.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12538834&dopt=Abstract

online pharmacies || Hair Million herbal formula for hair loss and hair growth || Tramadol || Antibiotics and prescription medications online literature || Antibiotics