Effect of Bile Salts on Partitioning Behavior and Gi Absorption of a Quaternary Ammonium Compound, Isopropamide Iodide

Gaginella, Timothy S.; Bass, Paul; Perrin, John H.; Vallner, J.J.

doi:10.1002/jps.2600620713

Cited by 28 publications

(14 citation statements)

References 18 publications

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“…3 and Fig. 5), probably due to increased lipophilicity by the ion-pair complexation, which is consistent with previous reports (Gaginella et al, 1973;Lee et al, 1978;Neubert, 1989;Van Gelder et al, 1999). The involvement of P-gp in the secretory transport of total berberine (i.e., berberine plus berberine-TDC ion-pair complex) across the Caco-2 cell monolayer was examined by measuring the transport of berberine in the presence of P-gp inhibitors.…”

Section: The Involvement Of P-gp In the Secretory Transport Of Berbersupporting

confidence: 89%

“…In general, organic cations (OCs) form lipophilic ion-pair complexes in the presence of certain organic anions (OAs), especially deoxyconjugated bile salts, resulting in an increase in gastrointestinal absorption and percutaneous passage of the OCs (Gaginella et al, 1973, Lee et al, 1978, Shim et al, 1981, Shim et al, 1986, Neubert, 1989, Van Gelder et al, 1999. Our group reported that the ionpair complexes of a quarternary ammonium compound, tributylmethylammonium (TBuMA), with taurodeoxycholate (TDC), a bile salt, significantly increased the affinity of TBuMA to P-gp (760 M versus 16.1 M for K m , P<0.01) (Song et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine

et al. 2008

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The objective of this study was to examine the effect of ion-pair complexation with endogenous bile salts on the transport of a quarternary ammonium organic cationic (OC) drug, berberine, across the Caco-2 and LLC-PK1 cell monolayers. The basolateral-to-apical (BL-AP) transport of berberine in Caco-2 cells was temperature dependent and 10-fold higher than that of the apical-to-basolateral (AP-BL) transport. Similar results were observed for the transport of berberine across the LLC-PK1 cells. Moreover, the BL-AP transport in the Caco-2 cells was significantly reduced by the cis-presence of P-glycoprotein (P-gp) inhibitors such as cyclosporine A, verapamil, and digoxin. These results suggest that an efflux transporter, probably P-gp, is involved in the Caco-2 cell transport. The K m and V max values for the carrier-mediated transport were estimated to be 83.4 mM and 7640 pmole/h/cm 2 , respectively. The apparent partition coefficient (APC) of berberine between n-octanol and a phosphate buffer (pH 7.4) was increased by the presence of an organic anion (OA), taurodeoxycholate (TDC, a bile salt), suggesting the formation of a lipophilic ion-pair complex between an OC (berberine) and an OA (TDC). Despite the ion-pair complexation, however, the BL-AP transport of berberine across the Caco-2 and LLC-PK1 cells was not altered by the cis-presence of bile salts or the rat bile juice. This is consistent with the reportedly unaltered secretory transport of a quarternary ammonium compound, tributylmethylammonium (TBuMA), across the Caco-2 cell monolayers in the cis-presence of bile salts or the rat bile juice, but not with our previous report in which the secretory transport of TBuMA across the LLC-PK1 cell was increased in the cis-presence of TDC. Therefore, the effect of ion-pair formation with the bile components or bile salts on the secretory transport of OCs appears to depend on the molecular properties of OCs (e.g., molecular weight, lipophilicity and affinity to relevant transporters) and the characteristics of cell strains (e.g., expression and contribution of responsible transporters to the transport).

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Section: The Involvement Of P-gp In the Secretory Transport Of Berbersupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine

et al. 2008

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“…However, literature information indicates the involvement of ion‐pair formation in the enhanced membrane permeability of cationic drugs. For example, ion‐pair formation of isopropamide with bile salts led to an enhancement in the transport across the gastrointestinal tract 24. A similar ion pair formation of organic cations and enhanced permeability was reported in the literature [e.g., propanetheline,25 bretylium,26 and AMD‐310027].…”

Section: Discussionsupporting

confidence: 62%

“…However, previous observations indicate that P‐gp is involved in the transport of TBuMA in the liver canalicular membrane13,16 and, thus, this transport mechanism may be responsible for the induced functional activity during the EHI. Secondary to this mechanism, other pathway(s), for example, BCRP (breast cancer resistance protein: ABCG2), a potential transporter for hydrophobic substrates,24 may also be involved. This aspect of TBuMA transport in the canalicular membrane is currently under investigation in this laboratory.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the Stationary Canalicular Excretion of Tributylmethyl Ammonium in Rats with a CCl4-Induced Acute Hepatic Injury

Choi

Song

Park

et al. 2005

Journal of Pharmaceutical Sciences

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“…The effect of sodium glycocholate upon the partitioning behavior and GI absorption of isopropamide iodide was studied (1101). Sodium glycocholate progressively increased the partitioning of isopropamide from a physiological aqueous buffer into n-octanol below the CMC of the bile salt, but increased partitioning was inhibited above this value.…”

Section: Biopharm Aceuticsmentioning

confidence: 99%

Pharmaceutical Sciences — 1973: Literature Review of Pharmaceutics

Herd¹,

Haleblian²

1974

Journal of Pharmaceutical Sciences

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Effect of Bile Salts on Partitioning Behavior and Gi Absorption of a Quaternary Ammonium Compound, Isopropamide Iodide

Cited by 28 publications

References 18 publications

Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine

Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine

Mechanism of the Stationary Canalicular Excretion of Tributylmethyl Ammonium in Rats with a CCl4-Induced Acute Hepatic Injury

Pharmaceutical Sciences — 1973: Literature Review of Pharmaceutics

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