Perivascular tissue pharmacokinetics of dipyridamole
PURPOSE: The tissue diffusivity (D(g)) and partitioning (K) for dipyridamole were determined and a model was developed to examine the relationship between perivascular dose and local dipyridamole tissue concentrations.
METHODS: Experiments were performed using an in vitro perfusion apparatus that recirculated buffer through different graft samples or normal porcine femoral arteries and veins. The grafts or blood vessels were immersed in a compartment containing Krebs-Henseleit (KH) buffer and dipyridamole (30 microg/mL). The recirculating buffer was sampled at multiple time points and dipyridamole was assayed. Estimates of the effective diffusivity (D(g)) and partition coefficient (K) of the drug in the vessel wall were determined and used to simulate dipyridamole tissue concentration after perivascular delivery.
RESULTS: Dipyridamole diffusivity within native femoral veins (D(g) = 3.87 +/- 0.93 x 10(-6) cm2/s) was approximately twice that within femoral arteries (D(g) = 2.06 +/- 0.79 x 10(-6) cm2/s, p < 0.01). Explanted grafts showed the lowest diffusivity. Partition coefficients of femoral arteries (K = 4.11 +/- 0.99) were higher than those of femoral veins (K = 2.05 +/- 0.85, p < 0.01) and explanted graft (K = 0.89 +/- 0.56, p < 0.01).
DISCUSSION: The results demonstrate that local drug kinetics vary greatly for different types of blood vessels and grafts. The pharmacokinetic parameters and resulting computational simulations are helpful in exploring perivascular drug delivery strategies.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2006 |
|---|---|
| Erschienen: |
2006 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
Pharmaceutical research - 23(2006), 4 vom: 19. Apr., Seite 718-28 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Goteti, Kosalaram [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 29.06.2006 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM161418317 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM161418317 | ||
| 003 | DE-627 | ||
| 005 | 20231223092137.0 | ||
| 007 | tu | ||
| 008 | 231223s2006 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0538.xml |
| 035 | |a (DE-627)NLM161418317 | ||
| 035 | |a (NLM)16552498 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Goteti, Kosalaram |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Perivascular tissue pharmacokinetics of dipyridamole |
| 264 | 1 | |c 2006 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 29.06.2006 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: The tissue diffusivity (D(g)) and partitioning (K) for dipyridamole were determined and a model was developed to examine the relationship between perivascular dose and local dipyridamole tissue concentrations | ||
| 520 | |a METHODS: Experiments were performed using an in vitro perfusion apparatus that recirculated buffer through different graft samples or normal porcine femoral arteries and veins. The grafts or blood vessels were immersed in a compartment containing Krebs-Henseleit (KH) buffer and dipyridamole (30 microg/mL). The recirculating buffer was sampled at multiple time points and dipyridamole was assayed. Estimates of the effective diffusivity (D(g)) and partition coefficient (K) of the drug in the vessel wall were determined and used to simulate dipyridamole tissue concentration after perivascular delivery | ||
| 520 | |a RESULTS: Dipyridamole diffusivity within native femoral veins (D(g) = 3.87 +/- 0.93 x 10(-6) cm2/s) was approximately twice that within femoral arteries (D(g) = 2.06 +/- 0.79 x 10(-6) cm2/s, p < 0.01). Explanted grafts showed the lowest diffusivity. Partition coefficients of femoral arteries (K = 4.11 +/- 0.99) were higher than those of femoral veins (K = 2.05 +/- 0.85, p < 0.01) and explanted graft (K = 0.89 +/- 0.56, p < 0.01) | ||
| 520 | |a DISCUSSION: The results demonstrate that local drug kinetics vary greatly for different types of blood vessels and grafts. The pharmacokinetic parameters and resulting computational simulations are helpful in exploring perivascular drug delivery strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Platelet Aggregation Inhibitors |2 NLM | |
| 650 | 7 | |a Dipyridamole |2 NLM | |
| 650 | 7 | |a 64ALC7F90C |2 NLM | |
| 650 | 7 | |a Polytetrafluoroethylene |2 NLM | |
| 650 | 7 | |a 9002-84-0 |2 NLM | |
| 700 | 1 | |a Masaki, Takahisa |e verfasserin |4 aut | |
| 700 | 1 | |a Kuji, Tadashi |e verfasserin |4 aut | |
| 700 | 1 | |a Leypoldt, John K |e verfasserin |4 aut | |
| 700 | 1 | |a Cheung, Alfred K |e verfasserin |4 aut | |
| 700 | 1 | |a Kern, Steven E |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmaceutical research |d 1984 |g 23(2006), 4 vom: 19. Apr., Seite 718-28 |w (DE-627)NLM012597236 |x 1573-904X |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2006 |g number:4 |g day:19 |g month:04 |g pages:718-28 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2006 |e 4 |b 19 |c 04 |h 718-28 | ||