[show abstract][hide abstract] ABSTRACT: The presence of five bisphenols, i.e., bisphenol F, bisphenol A, bisphenol B, bisphenol F diglycidyl ether, and bisphenol A diglycidyl ether, was monitored in commercial milk packed in plastic bottles marketed in Italy. The new validated method includes a solid-phase extraction procedure followed by liquid chromatography with fluorescence detection. All positive results were confirmed by liquid chromatography-tandem mass spectrometry analysis. The limits of detection and quantification and the recovery percentages indicated that the method is suitable for detecting bisphenols in milk at concentrations far below the legal limits. Of 68 commercial milk samples analyzed, no bisphenol was found in 27 samples (39.7%), and 41 samples (60.3%) contained one or more bisphenols. The bisphenol most frequently found was bisphenol F (36 samples, 52.9%) followed by bisphenol A (20 samples, 29.4%) and bisphenol B (6 samples, 8.8%). Taking into consideration the limits of detection, no sample contained either bisphenol F diglycidyl ether or bisphenol A diglycidyl ether.
Journal of food protection 09/2013; 76(9):1590-6. · 1.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: Glatiramer acetate (GA) is an approved and well tolerated drug for the treatment of relapsing-remitting multiple sclerosis. We report a case of a 52year-old man with psoriasis and relapsing-remitting multiple sclerosis who developed, after 21months of GA treatment, an injection-site cutaneous necrosis that involved both subcutaneous and muscular tissue with massive edema, followed, 3days later, by radial nerve palsy. After few days another similar lesion appeared in another injection-site. We hypothesize that cutaneous necrosis could be due to a local dis-immune reaction and, probably, psoriasis could have played an important role in its pathogenesis.
Journal of the neurological sciences 06/2013; · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background. Few data exist on the prevalence of FSD in thyroid disorders. Aim. We evaluated FSD in women with thyroid diseases and in control age matched healthy women to investigate the relationship between sexual function, and thyroid hormones. Methods. One hundred and four women with thyroid diseases and 53 controls participated in the study. Eighteen with hyperthyroidism (Group1), 22 hypothyroidism (Group2), 45 Hashimoto's thyroiditis (Group3), 19 nodular goiter (Group4) underwent thyroid function evaluation and sonography. The Female Sexual Function Index (FSFI) assessed sexual function. Results. The prevalence of FSD was 46.1% in thyroid diseases and 20.7% in controls. Only in Group4, the prevalence (68.4 %) was significantly higher than in controls (P < 0.005). The mean total FSFI score were 20.1±7.1 in women with thyroid diseases and 25.6±4.7 in the controls (P<0.001). Compared with controls, there was a significant decrease of desire in Group2; desire, arousal and lubrication in Group3; desire, arousal, lubrication, orgasm and satisfaction in Group4. In thyroid diseases the prevalence of FSD was 53% and 42%, while in the controls was 55% and 20%, in menopausal and pre-menopausal groups, respectively. We found a significant inverse correlation between TSH and FSFI (r =-0.7, P= 0.01) in Group 4, which showed the lowest FSFI score (17.8±5.7) and the highest BMI (28.4±7.1 Kg/m2).Conclusions: Women with thyroid diseases present a higher prevalence of FSD than controls. Although our findings suggest a higher impairment of sexual function in Group4 and a role for TSH in FSD, further researches are needed.
Journal of endocrinological investigation 04/2013; · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by resident intestinal bacteria. In patients with chronic kidney disease, the accumulation of p-cresol and of its metabolite p-cresyl-sulphate causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies to reduce plasma p-cresol levels are highly demanded but not available yet. Because it has been reported that the phosphate binder sevelamer sequesters p-cresol in vitro we hypothesized that it could do so also in peritoneal dialysis patients. To explore this hypothesis we measured total cresol plasma concentrations in 57 patients with end-stage renal disease on peritoneal dialysis, 29 receiving sevelamer for the treatment of hyperphosphatemia and 28 patients not assuming this drug. Among the patients not assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12 received no drug because they were not hyperphosphatemic. Patients receiving sevelamer had plasma p-cresol and serum high sensitivity C-reactive protein concentrations significantly lower than those receiving lanthanum or no drug. Conversely, no difference was observed among the different groups either in residual glomerular filtration rate, total weekly dialysis dose, total clearance, urine volume, protein catabolic rate, serum albumin or serum phosphate levels. Multiple linear regression analysis showed that none of these variables predicted plasma p-cresol concentrations that, instead, negatively correlated with the use of sevelamer. These results suggest that sevelamer could be an effective strategy to lower p-cresol circulating levels in peritoneal dialysis patients in which it could also favorably affect cardiovascular risk because of its anti-inflammatory effect.
PLoS ONE 01/2013; 8(8):e73558. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Alzheimer's disease (AD) is characterized by irreversible and progressive loss of memory and cognition and profound neuronal loss. Current therapeutic strategies for the treatment of AD have been directed to a variety of targets with the aim of reversing or preventing the disease but, unfortunately, the available treatments often produce no significant clinical benefits. During the last decades compounds that inhibit or modulate γ-secretase, reducing β amyloid (Aβ) levels, have been considered as potential therapeutics for AD. Among these the (R)-enantiomer of flurbiprofen (FLU) seems to be very promising, but it shows low brain penetration. In this study, in order to improve the properties of FLU against Alzheimer's pathogenesis we synthesized some novel FLU lipophilic analogues. Lipophilicity of the new molecules has been characterized in terms of clogP, log KC18/W and log K IAM/W values. Permeability has been determined in both gastrointestinal PAMPA (PAMPA-GI) at different pH values and in brain blood barrier PAMPA (PAMPA-BBB) models. They were also tested for their ability to inhibit in vitro γ-secretase activity using rat CTXTNA2 astrocytes. Interestingly, the investigated molecules demonstrated to reduce Aβ 42 levels without affecting the amyloid precursor protein APP level in a clear concentrations-dependent manner.
[show abstract][hide abstract] ABSTRACT: Opportunistic infections are frequently reported to induce movement disorders in late stages of HIV. We report a case of a 32-year-old woman who presented headache and fever that was resistant to antipyretic drugs and to common antibiotics. Hereafter her right limbs were affected by several hyperkinetic movement disorders (ballismus, chorea, dystonia, athetosis). Brain MRI showed a mass lesion involving left basal ganglia. Serological tests were positive for HIV and for Toxoplasma gondii. Clinical features, therapeutical approaches, prognostic factors and possible pathogenesis are discussed.
A literature review of cases of movement disorders associated with AIDS is provided.
[show abstract][hide abstract] ABSTRACT: The membrane phospholipid affinity data, logk(w)(IAM), for 18 acidic and unionized drugs spanning a wide lipophilicity range were measured by HPLC on two different phospholipid stationary phases, i.e. IAM.PC.MG and IAM.PC.DD2. These data related weakly with both logP(N) values, the n-octanol/water partition coefficients of the neutral forms, and logD(7.4) values, the n-octanol/water partition coefficients of the mixtures of neutral and ionized forms at pH 7.4. The lack of collinearity confirms that, differently from partition in n-octanol/water, partition in phospholipids encodes not only lipophilic/hydrophobic intermolecular recognition forces but also ionic bonds, due to electrostatic interactions between electrically charged species and phospholipids, according to the "pH piston hypothesis". Since, differently from bases, electrostatic interactions between acids and phospholipids take place at the surface of phospholipid layers (choline moieties), and not near their lipophilic core (phosphate moieties), they were parameterized by a new procedure yielding "Δ(')logk(w)(IAM)" parameters, i.e. the difference between the IAM retention factors observed for the analytes and those of neutral compounds with the same n-octanol partition values displayed by the analytes at pH 7.4. All acidic analytes, but one, and all unionized analytes, but the unionizable ones, showed positive Δ(')logk(w)(IAM) values, indicating that they partition stronger in phospholipids than in n-octanol. LogBB values (capability to pass BBB) weakly related with both lipophilicity and phospholipid affinity values; in contrast they are inversely related with Δ(')logk(w)(IAM) values. The relationships between logBB and Δ(')logk(w)(IAM) practically overlapped the previously found logBB/Δlogk(w)(IAM) relationships for bases. The excess of polar interaction component between acidic drugs and phospholipids, mainly electrostatic forces, although enhancing partition in phospholipids, hinders membrane passage, analogously to the behavior previously reported for bases. The study suggests that IAM-HPLC is an effective technique to perform simple and fast measurements of the intermolecular recognition forces related to membrane partition and permeation. This can contribute to better understand the mechanisms governing both partition of charged species in cell membranes and passage through them, also allowing the possible optimization of the pharmacokinetic properties of the drugs at the early stages of their development.
Journal of pharmaceutical and biomedical analysis 12/2012; 75C:165-172. · 2.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Multiple endocrine neoplasia syndromes have since been classified as types 1 and 2, each with specific phenotypic patterns. MEN1 is usually associated with pituitary, parathyroid and paraneoplastic neuroendocrine tumours. The hallmark of MEN2 is a very high lifetime risk of developing medullary thyroid carcinoma (MTC) more than 95% in untreated patients. Three clinical subtypesdMEN2A, MEN2B, and familial MTC (FMTC) have been defined based on the risk of pheochromocytoma, hyperparathyroidism, and the presence or absence of characteristic physical features). MEN2 occurs as a result of germline activating missense mutations of the RET (REarranged during Transfection) proto-oncogene. MEN2-associated mutations are almost always located in exons 10, 11, or 13 through 16. Strong genotype-phenotype correlations exist with respect to clinical subtype, age at onset, and aggressiveness of MTC in MEN2. These are used to determine the age at which prophylactic thyroidectomy should occur and whether screening for pheochromocytoma or hyperparathyroidism is necessary. Specific RET mutations can also impact management in patients presenting with apparently sporadic MTC. Therefore, genetic testing should be performed before surgical intervention in all patients diagnosed with MTC. Recently, Pellegata et al. have reported that germline mutations in CDKN1B can predispose to the development of multiple endocrine tumours in both rats and humans and this new MEN syndrome is named MENX and MEN4, respectively. CDKN1B. A recent report showed that in sporadic MTC, CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker. New insights on MEN syndrome pathogenesis and related inherited endocrine disorders are of particular interest for an adequate surgical and therapeutic approach.
Il Giornale di chirurgia 11/2012; 33(11/12):370-373.
[show abstract][hide abstract] ABSTRACT: The membrane phospholipid affinity data, log k(w)(IAM), for 14 basic drugs spanning a wide lipophilicity range were measured by HPLC on two different phospholipid stationary phases, i.e. IAM.PC.MG and IAM.PC.DD2. These data related weakly with log P(N) values, the n-octanol/water partition coefficients of the neutral forms; poorer relationships were found with log D(7.0) values, the n-octanol/water partition coefficients of the mixtures of neutral and ionized forms at pH 7.0. The lack of collinearity confirms that, differently from partition in n-octanol/water, partition in phospholipids encodes not only lipophilic/hydrophobic intermolecular recognition forces but also ionic bonds, due to electrostatic interactions between electrically charged species and phospholipids, according to the "pH-piston hypothesis". This component of interaction was parameterized by Δ log k(w)(IAM) values; they are the differences between the log k(w)(IAM) values experimentally measured and the values expected for neutral isolipophilic compounds. Δ log k(w)(IAM) values of the various analytes changed almost linearly from positive to negative values at increasing lipophilicity. This behavior is consistent with an interaction mechanism with membrane phospholipids including two intermolecular interaction forces: (i) lipophilic/hydrophobic interactions, which decrease on ionization proportionally to the lipophilicity of the neutral forms, and (ii) electrostatic interactions, which increase on ionization and are quite constant for all the analytes at a given ionization degree. Since BBB passage of the considered compounds is supposed to be based on passive mechanisms, we investigated the possible relationships between log BB values, i.e. the logarithms of the ratio between brain and blood concentrations, and three physico-chemical parameters, i.e. (i) log P(N) (lipophilic interaction of the neutral form), (ii) log k(w)(IAM) (global interaction with phospholipids), and (iii) Δ log k(w)(IAM) (electrostatic component of interaction with phospholipids). The results suggest that the electrostatic interactions encoded in log k(w)(IAM) values might act as trapping forces in a phospholipid barrier. Actually, we observed an inverse linear dependence of log BB on Δ log k(w)(IAM) values, but only for the compounds showing positive Δ log k(w)(IAM) values. We conclude that the driving force for BBB passage is the lipophilicity of the neutral forms, log P(N), and not the lipophilicity actually displayed at the experimental pH, log D(7.0). Indeed, the latter does not adequately take into account the role played by protonation in the analyte/membrane interactions because protonation, although hindering membrane passage, can either reduce or enhance partition in phospholipids, depending on analyte lipophilicity.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 04/2012; 45(5):685-92. · 2.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: This work proposes a new capillary electrochromatography (CEC) method for determination of drug partition in membrane phospholipids. CEC experiments were carried out in a 100 μm (ID) fused-silica capillary, partially packed with a chromatographic phospholipid stationary phase, so-called Immobilized Artificial Membrane, IAM.PC.DD2. The observed retention values were corrected by both the electro-osmotic and electrophoretic mobility values, measured by capillary electrophoresis (CE) experiments, assuming the values of the logarithms of "chromatographic" affinity factors, log k(CEC) as indexes of affinity for phospholipids. Analogously to biochromatography, all the values were determined with a totally aqueous mobile phase, or extrapolated to 100% aqueous buffer. The analytes were 16 structurally unrelated compounds, of basic, neutral, and acidic nature. To evaluate the effectiveness of CEC data to describe partition in phospholipids, log k(CEC) were related to both log P and log k(w)(IAM) values. log P are the lipophilicity values expressed as the logarithms of n-octanol/water partition coefficients and log k(w)(IAM) are the retention data measured by High Performance Liquid Chromatography (HPLC) on an IAM.PC.DD2 column, assumed as the reference values for phospholipid affinity. Phospholipid affinity scale by CEC related to that achieved by HPLC, but only if two different subclasses were considered separately, i.e. protonated and unprotonated analytes; indeed, all the compounds protonated at the experimental pH value (7.0) were retained stronger in CEC than in HPLC. This discrepancy may be due to the use of different buffers in CEC and HPLC since, to avoid the occurrence of a high current, the eluent in CEC experiments was of different composition and lower ionic strength than in HPLC. CEC analyses were faster and required lower amounts of both solvent and stationary phase than HPLC; moreover, with the exception of only three analytes, all analyses were performed with 100% aqueous eluents avoiding time-consuming and tedious extrapolation procedures.
Journal of pharmaceutical and biomedical analysis 04/2011; 54(5):893-9. · 2.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: The enantioselective retention of thirteen beta-blockers on HPLC stationary phases supporting human serum albumin (HSA) or alpha(1)-acid glycoprotein (AGP) was investigated. Eight beta-blockers were enantiomerically resolved on the AGP column whereas only four beta-blockers were resolved on the HSA column. Moreover, interactions between beta-blockers and AGP were much stronger than those with HSA. Retention values on both HSA and AGP for less retained enantiomers related well with various lipophilicity parameters, with the best relationships found with log k(w)(IAM) values obtained on HPLC stationary phases supporting phospholipids, i.e. the so-called Immobilized Artificial Membrane (IAM). Differently from n-octanol lipophilicity values, these values encode both lipophilic. Electrostatic intermolecular recognition forces which may be involved in the interaction between ionized analytes, such as beta-blockers, and proteins. However, their effectiveness to describe non-specific interactions with serum-proteins for other classes of drugs needs further investigations. Analyses performed on AGP with eluent containing dimethyloctylamine (DMOA) as the displacer demonstrated that enantioselective sites bind to both (-)-forms and (+)-forms, but the binding to (-)-forms is stronger. The enantiomer competition to bind to a same site may be relevant from a pharmacokinetic point of view when racemic mixtures are administered. Finally, in contrast to previously reported data in the literature, we found that AGP can bind enantioselectively not only the more lipophilic congeners but also the less lipophilic ones.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 09/2009; 38(5):472-8. · 2.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bisphenol A (BPA) and bisphenol B (BPB) concentrations were determined in peeled canned tomatoes of different brands bought in Italian supermarkets. Tomato samples analyzed were packaged in cans coated with either epoxyphenolic lacquer or low BADGE enamel. A solid phase extraction (SPE) was performed on C-18 Strata E cartridge followed by a step on Florisil cartridge. Detection and quantitation were performed by a reversed phase high-performance liquid chromatography (RP-HPLC) method with both UV and fluorescence detection (FD). On the total of 42 tested tomato samples, BPA was detected in 22 samples (52.4%), while BPB was detected in 9 samples (21.4%). BPA and BPB were simultaneously present in 8 of the analyzed samples. The levels of BPA found in this study are much lower than the European Union migration limits of 3 mg/kg food and reasonably unable to produce a daily intake exceeding the limit of 0.05 mg/kg body weight, established by European Food Safety Authority.
Journal of Agricultural and Food Chemistry 11/2008; 56(22):10633-7. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abstract The effect of ricinoleic acid on nitric oxide synthase (NOS) activity has been investigated in the rat. NOS, determined by the oxidation of oxyhemoglobin to methemoglobin or by the formation of citrulline, was detected in homogenates of both ileal and colonic tissue. Ricinoleic acid (10−5–10−3 M) incubated with intestinal tissue for 15 min, increased NOS activity (P <0.05–0.01); however the effect was more evident in the ileum than in the colon. A pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 6.25–25 mg kg−1 i.p., 15 min before the removal of tissue) inhibited the increase in NOS activity (P < 0.05). These findings confirm an involvement of NO in the laxative effect of ricinoleic acid (castor oil).
[show abstract][hide abstract] ABSTRACT: Minocycline is a widely used antibacterial agent. Moreover, it is also demonstrated to be effective in several neurodegenerative disorders, due to its antioxidant and anti-inflammatory activities. However, the last activity is only apparent at very high doses. In fact, minocycline poorly crosses the blood-brain barrier (BBB) due to its low lipophilicity and half-life. The present work details the physicochemical characterization of a series of alkanoyl-10-O-minocycline derivatives (2-6), which are able to produce self-assembled aggregates in aqueous solution. The n-octanol/aqueous phase lipophilicity of minocycline and its derivatives were assessed by theoretical calculation, by shake-flask method, and by reversed-phase HPLC. Moreover, we determined their affinity for membrane phospholipids measuring their HPLC retention on phospholipid-based stationary phases, the so-called "Immobilized Artificial Membranes" (IAMs). Our results indicate high lipophilicity values for the minocycline derivatives (compounds 2-6); these values and the corresponding phospholipid affinities increase with the length of the hydrocarbon moiety substituent. Furthermore, the ability of the investigated alkanoyl-10-O-minocycline derivatives to self-assemble could allow a direct administration by oral and intraperitoneal routes as supramolecular systems. The advantages are an enhancement of drug solubilization, a sustained release, and the consequent less frequent drug administration. Moreover, we can hypothesize the potential solubilization in the micellar core of other poorly water soluble drugs which could improve the therapeutic effects of the pharmaceutical formulation in a combined therapy. Given the high lipophilicity of the title derivatives, they can be supposed to offer higher half-life and a better BBB penetration than minocycline. Since the new derivatives retain the structural features related to the antioxidant and anti-inflammatory effects of minocycline, they can be regarded not only as long-acting antimicrobial agents but also as candidate drugs for a targeted treatment of mental illness.
European Journal of Pharmaceutical Sciences 08/2008; 34(2-3):118-28. · 2.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: The membrane phospholipid affinity of ten quinolone antibacterial agents, including both acidic and zwitterionic compounds, was measured by HPLC on two different immobilized artificial membrane (IAM) stationary phases, namely IAM.PC.MG and IAM.PC.DD2; it is expressed as the logarithm of the retention factor measured with (or extrapolated to) 100% aqueous eluent at pH 7.0, logk(w)(IAM). Quinolones are a class of highly potent, orally active, broad-spectrum antibacterial agents. For these compounds, lipophilicity values in n-octanol found in the literature, either calculated or measured, are not consistent with each other and are too low to be compatible with their pharmacokinetic properties. The logk(w)(IAM) values obtained in this study showed no relation with any of the lipophilicity values in the literature (clogP(a), clogP(b), MLP, logD(7.4)). In contrast, they were collinear with a new lipophilicity scale we had previously obtained by an original ion-pair reversed-phase HPLC method set up to estimate the lipophilicity of the neutral forms, logP(N). Moreover, when comparing the retention of quinolones on IAM to the retention of structurally unrelated neutral compounds, we observed that they interact with phospholipids with the same affinity as neutral isolipophilic compounds. The use of an eluent at pH 5.5, instead of pH 7.0, increased the retention on IAM not only for acidic, but also for zwitterionic congeners, indicating that phospholipid affinity is enhanced in the experimental conditions that depress the ionization of the acidic function, even when the ionization of the amino function increases simultaneously. To gain an insight into the mechanism of quinolones/serum-protein interactions, we investigated about possible relationships between quinolones affinity data for serum proteins and IAM data. Quinolone affinity for both HSA and AGP was already demonstrated poorly related to n-octanol lipophilicity values, probably due to the occurrence of electrostatic interactions. Only poor relationships were found between IAM and HSA affinity data, whereas quite good relationships were found with AGP affinity data. However, IAM.PC.DD2 data correlated better than those on IAM.PC.MG with quinolone affinity for both serum-proteins, mainly due to the fact that IAM.PC.MG phase is scarcely discriminative for the compounds with the highest retention values. The results suggest that IAM retention can produce a lipophilicity scale that, unlike solvent/water partition coefficients, is consistent with the pharmacokinetic behaviour of zwitterionic quinolones.
European Journal of Pharmaceutical Sciences 09/2007; 31(5):288-97. · 2.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: The retention of 10 quinolone antibacterial agents on HPLC stationary phases supporting human serum albumin (HSA) or alpha(1)-acid glycoprotein (AGP) was investigated. Among ofloxacine and flumequine, the two chiral compounds in the selected set, only the latter showed a split chromatographic peak and only on HSA but not on AGP, indicating that enantioselective specific sites play only a minor role in the retention. The retention of quinolones, which included four acidic and six zwitterionic congeners, was correlated with various lipophilicity scales: (i) theoretically calculated values, clogP, (ii) values measured at pH 7.4 by the shake-flask method, logD(7.4), and (iii) values extrapolated by retention data measured by ion-pair reversed-phase high performance liquid chromatography (RP-HPLC). We assumed that the latter values, logP(i.p.), were close to the lipophilicity of the neutral forms, logP(N), for both acidic and zwitterionic congeners. No relationship was found between retention on serum proteins and clogP values, whereas a reasonable relationship was found with logD(7.4) values, but only when the two subclasses, acidic and zwitterionic congeners, were considered separately. The relationship between retention data on serum proteins and logP(i.p.) values indicated that the affinity for serum proteins depends on the lipophilicity of the neutral forms only for logP values up to 1.5. Above this value, protein retention does not further increase, becoming almost constant. Based on both the observations above reported and the small values of the slopes of regression equations, we conclude that the interaction of the more lipophilic quinolones, mainly the zwitterions, with serum proteins is not governed uniquely by lipophilicity but also by other mechanisms, probably of electrostatic nature.
European Journal of Pharmaceutical Sciences 04/2007; 30(3-4):211-9. · 2.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: This review discusses Immobilised Artificial Membrane (IAM) HPLC technique in terms of the structure of IAM phases, experimental methods, and information content. In a first part, the relations between pharmacokinetics and lipophilicity are discussed. Lipophilicity in n-octanol of ionisable compounds is shortly examined as a base for further discussion. Particular emphasis is placed on the meaning of phospholipids as partition phases and on the HPLC partitioning techniques. The next part presents structural information on IAM columns. The influence of experimental conditions on IAM-HPLC parameters is also examined. Particular attention is paid to the relations between IAM data and other lipophilicity parameters: IAM data are compared to lipophilicity in n-octanol and partition in liposomes. In the last part, the effectiveness of IAM data to predict bioactivity data is discussed in terms of relationships found with data of i) permeability across Caco-2 cells and passive intestinal absorption, ii) penetration across the blood-brain barrier, iii) pharmacokinetics, iv) various other pharmacological activities, and v) transdermal transport. Based on the studies reported, IAM-HPLC appears as a suitable technique to achieve data of partition in biomembranes. As compared to lipophilicity in n-octanol, IAM data for ionised compounds are distinctive. As compared to partition in liposomes, IAM technique is much faster and more reproducible.
Current Computer - Aided Drug Design 11/2006; 2(4):341-352. · 1.54 Impact Factor