Adnan Badwan 1, Maya, " Enhancement of Oral Absorption of Insulin in Humans " , "Neuroendocrinology Letters",Vol.,No., , , 02/02/2009
Objective: the purpose of this study is to investigate oral absorption of 1, 2 and 3 U/kg oral insulin five test products with different particle sizes in comparison with 0.1 U/kg subcutaneous reference formulation. Methods: Twenty five healthy volunteers participated in five studies using a two-phase, two-sequence crossover design with washout period of one day. Mean disposition kinetics was determined by non-compartmental analysis using Kinetica program. Absorption kinetics of insulin products were then determined using SIMCYP simulator utilizing ADAM model. Results & conclusions: Dimensional analysis results showed the superiority of formula 4: 2 U/kg oral dose with 57 nm particle size over other oral formulations when compared with subcutaneous route. Optimized intestinal permeability coefficients (x10-4) of insulin best test and reference formulations were 0.051 and 0.179 cm/sec respectively. Total fraction of insulin dose absorbed (Fa) for the test and reference products were 3.0 % and 19 % respectively. Subcutaneous product exhibited higher absorption rate and extent than oral insulin. Yet that was compensated by the increase in other factors such as Fa*, Peff* and oral dose, leading to similar insulin plasma levels and similar effect on glucose infusion rates. Oral insulin bioavailability was shown promising for the development of oral insulin product.
Nasir M. Idkaidek1* , " Effect of Truncated AUC Method on the Bioequivalence of High and Low Variable Drugs in Humans " , "Acta Pharmaceutica Sciencia",Vol.50,No., , , 04/06/2008
Objective: The purpose of this study is to investigate the effect of using truncated area under the curve AUC) method on the bioequivalence of high and low variable drugs with long half lives in healthy volunteers. Materials and Methods: Model low and high variable drugs used are Tamoxifen ( CV < 30 % , with mean half live of > 100 hr) and Flouxitine Tamoxifen ( CV > 30 % , with mean half live of > 45 hr) respectively. 24 healthy subjects participated in each study using cross over design. Individual disposition kinetic parameters of AUC0 -t, AUC0 - ∞, Cmax, Tmax and half life were calculated by non-compartmental analysis using Kinetica program for both studies using all data points and using truncated AUC method. Results: No statistical significant differences were obtained between parameters Cmax and Tmax suggesting similar rate of drug absorption in both methods, which is expected. However, AUC0 -t, AUC0- ∞ and half life values were statistically lower (P < 0.05) in the truncated AUC method for both drugs, which is also expected since shorter time interval was used for calculations. In addition, the 90 % confidence intervals for log-transformed AUC0 -t, AUC0 - ∞, and Cmax falled within the accepted 80 – 125 % in both methods. Conclusion: These results are in agreement with the US FDA guidelines that recommend using truncated AUC method for long half life drugs, which saves time and money.
Nasir Idkaidek and T, " Effect of microgravity on ibuprofen pharmacokinetics in humans " , "J Clinic Pharmacol",Vol.,No., , , 12/01/2011
Pharmacokinetics of ibuprofen was studied under microgravity (μG) conditions and compared to those at normal gravity (1G) in humans. 6 healthy human volunteers were given 600 mg oral dose ibuprofen during 1-day simulated μG anti-orthostatic bed rest position (ABR), then at normal position (1G) in sequential design with 7 days washout time. Saliva and plasma samples were obtained up to 8 hours after dosing. Ibuprofen was not detected in all saliva samples. Pharmacokinetic parameters in plasma were calculated by either non compartmental analysis or one compartment model using Kinetica program. Absorption kinetic parameters were then predicted by ADAM and PE modules using Simcyp program. Results have showed increased rate of ibuprofen dissolution and absorption; and hence faster onset of action under uG conditions. However, rate of drug elimination and bioavailability was not affected by uG, suggesting no need for dose adjustment.
Salem II, Najib NM, , " A retrospective, open-label analysis of the population pharmacokinetics of a single 10-mg dose of loratadine in healthy white Jordanian male volunteers. " , "Clin Ther",Vol.32,No.2, , , 02/01/2010
Background: Loratadine is a long-acting tricyclic antihistamine with selective peripheral histamine H1-receptor antagonistic activity. Loratadine is rapidly absorbed following oral administration of 10 mg tablets, once daily for 10 days to healthy adult subjects with times to maximum concentration (Tmax) of 1.3 hours for loratadine and 2.5 hours for its major active metabolite, descarboethoxyloratadine.
The purpose of this study is to determine the population pharmacokinetics of loratadine after oral administration.
72 healthy male subjects gave written informed consent to participate in such studies before screening. Studies were approved by the Institutional Review Board. The studies were performed in accordance with the declaration of Helsinki (Washington, USA, 2002) and current GCP guidelines. Subjects, age 23 ± 3.57 years, were within 15 % of their ideal body weight and were judged to be healthy based on medical history, physical examination, complete blood count and serum chemistry. Following a ten-hour overnight fast, a single oral dose of 10 mg loratadine tablets were administered orally followed by 240-ml water. Blood samples were collected in heparinized tubes at pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 & 96 hours after dosing. Blood samples were harvested to plasma and stored at –20 0C until analyzed by a validated liquid chromatography- mass spectrometry (LCMSMS) technique. Mean & population plasma level profiles were examined Simultaneous data fitting of all individuals was done using Kinetica® program version 4.1.
The results proved the validity of this specific and sensitive method for the intended use. The method was proved linear over the range of concentration 0.10-20.00 ng/ml (r>0.999). The lower limit of quantification was proved to be 0.1 ng/ml with 95% accuracy; while precision as CV was 7.44%. Intra-day accuracy ranged 91.9 - 97.2% at high and low QCs, respectively. Whereas inter-day accuracy ranged between 93.57 (CV 4.35%) and 98.78% (CV 5.78%). Population elimination and absorption rate constants and half life values were 0.19 hr-1, 3.65 hr, 1.31 hr-1 and 0.53 hr respectively. Moreover, Distribution and redistribution rate constants and lag time were 0. 31 hr-1, 0.02 hr-1 and 0.32 hr respectively. The non-compartmental estimate of maximum drug concentration was 3.02 ng/ml and occurred after 1.30 hr.
Population pharmacokinetic parameters for loratadine were essentially uncovered. The population elimination half-life value for loratadine was proved to be 3.65 hours.
Ehab Abu-Basha, Nasi, " Pharmacokinetics and bioavailability of sulfadiazine and trimethoprim " , "J. vet. Pharmacol. Therap",Vol.7,No.4, , , 12/01/2006
A pharmacokinetic and bioavailability study of sulfadiazine combined with
trimethoprim (sulfadiazine ⁄ trimethoprim) was carried out in fifteen healthy
young ostriches after intravenous (i.v.), intramuscular (i.m.) and oral
administration at a total dose of 30 mg⁄kg body weight (bw) (25 and 5 mg ⁄kg
bw of sulfadiazine and trimethoprim, respectively). The study followed a single
dose, three periods, cross-over randomized design. The sulfadiazine ⁄ trimethoprim
combination was administered to ostriches after an overnight fasting on
three treatment days, each separated by a 2-week washout period. Blood
samples were collected at 0 (pretreatment), 0.08, 0.25, 0.50, 1, 2, 4, 6, 8, 12,
24 and 48 h after drug administration. Following i.v. administration, the
elimination half-life (t1 ⁄ 2b),
Eyad M Mallah1*, Moh, " Plasma concentrations of 25-hydroxyvitamin D " , "",Vol.,No., , , 08/01/2011
Background: Vitamin D is cutaneously synthesized following sun exposure (vitamin D3) as well as it is derived
from dietary intake (vitamin D3 and D2). Vitamin D2 and D3 are metabolized in the liver to 25-hydroxyvitamin D (25
(OH)D). This metabolite is considered the functional indicator of vitamin D stores in humans. Since Jordan latitude
is 31°N, cutaneous synthesis of vitamin D3 should be sufficient all year round. However, many indications reveal
that it is not the case. Thus, this study was conducted to determine the 25(OH)D status among Jordanians.
Methods: Three hundred healthy volunteers were enrolled in a cross sectional study; 201 females and 99 males. 25
(OH)D and calcium concentrations were measured by enzyme linked immunosorbent assay and spectroscopy
techniques, respectively. All participants filled a study questionnaire that covered age, sex, height, weight, diet, and
dress style for females. Females were divided according to their dress style: Western style, Hijab (all body parts are
covered except the face and hands), and Niqab (all body parts are covered including face and hands).
Results: The average plasma 25(OH)D levels in males and females were 44.5 ± 10.0 nmol/l and 31.1 ± 12.0 nmol/l,
respectively. However, when female 25(OH)D levels were categorized according to dress styles, the averages
became 40.3, 31.3 and 28.5 nmol/l for the Western style, Hijab and Niqab groups, respectively. These 25(OH)D
levels were significantly less than those of males (p < 0.05, 0.001, 0.001, respectively). In addition, the plasma 25
(OH)D levels of the Western style group was significantly higher than those of Hijab and Niqab groups (p < 0.001).
Furthermore, dairy consumption in males was a positive significant factor in vitamin D status. Even though calcium
concentrations were within the reference range, the Hijab and Niqab-dressed females have significantly less plasma
calcium levels than males (p < 0.01).
Conclusions: Very low plasma 25(OH)D levels in females wearing Hijab or Niqab are highly attributed to low
sunlight or UVB exposure. In addition, most of males (76%) and Western style dressed females (90%) have 25(OH)D
concentrations below the international recommended values (50 nmol/l), suggesting that although sun exposure
should be enough, other factors do play a role in these low concentrations. These findings emphasize the
importance of vitamin D supplementation especially among conservatively dressed females, and determining if
single nucleotide polymorphisms of the genes involved in vitamin D metabolism do exist among Jordanians
Nasir M Idkaidek, Ph, " Metformin IR versus XR Pharmacokinetics in Humans " , "",Vol.,No., , , 11/01/2011
Pharmacokinetics of metformin extended release (XR) formulation were studied under
fasting and fed conditions and compared to those of immediate release (IR) under fasting conditions in
humans. 78 healthy human volunteers participated in 3 independent studies (26 subjects per study)
were given either 1000 mg oral dose metformin IR or 750 mg metformin XR. Plasma samples were
obtained up to 24 hours after dosing. Pharmacokinetic parameters in plasma were calculated by non
compartmental analysis using Kinetica program. Results have shown increased XR bioavailability and
delayed time to reach the maximum concentration (Cmax ) in the fed state as compared to fasted state,
with no significant difference in Cmax and half life values. On the other hand, the IR formulation
showed significant differences in all parameters as compared to XR formulation, yet the half life was
similar. In conclusion, XR formulation was shown superior to IR formulation with less possible side
Nasir Idkaidek* and , " Saliva versus Plasma Pharmacokinetics, Theory and Application of a Salivary Excretion Classification System " , "Molecular Pharmaceutics",Vol.,No., , , 07/23/2012
Aims: to study pharmacokinetics of randomly selected drugs in plasma and saliva samples in healthy human volunteers, and to introduce a salivary classification system.
Methods: Saliva and plasma samples were collected for 3-5 half life values of sitagliptin, cinacalcet, metformin, montelukast, tolterodine, hydrochlorothiazide (HCT), lornoxicam, azithromycin, diacerhein, rosuvastatin, cloxacillin, losartan and tamsulosin after oral dosing. Saliva and plasma pharmacokinetic parameters were calculated by non compartmental analysis using Kinetica program. Effective intestinal permeability (Peff) values were estimated by Nelder-Mead algorithm of the Parameter Estimation module using SimCYP program. Peff values were optimized to predict the actual average plasma profile of each drug. All other physicochemical factors were kept constant during the minimization processes.
Results: sitagliptin, cinacalcet, metformin, tolterodine, HCT, azithromycin, rosuvastatin and cloxacillin had salivary excretion with correlation coefficients of 0.59 - 0.99 between saliva and plasma concentrations. On the other hand, montelukast, lornoxicam, diacerhein, losartan and tamsulosin showed no salivary excretion. Estimated Peff ranged 0.16 – 44.16 X10-4 cm/sec, while reported fraction unbound to plasma proteins (fu) ranged 0.01 -0.99 for the drugs under investigation. Saliva/plasma concentrations ratios ranged 0.11 – 13.4, in agreement with drug protein binding and permeability. A Salivary Classification System (SCS) was suggested based on drug high (H)/low (L) permeability and high (H)/low (L) fraction unbound to plasma proteins, which classifies drugs into 4 classes. Drugs that fall into class I (H/H), II (L/H) or III (H/L) are subjected to salivary excretion, while those falling into class IV (L/L) are not. Additional data from literature was also analyzed and all results were in agreement with the suggested SCS. Moreover, a polynomial relationship with correlation coefficient of 0.99 is obtained between S* and C*, where S* and C* are saliva and concentration dimensionless numbers respectively.
Conclusions: The suggested Salivary Classification System (SCS) can be used as a guide for drug salivary excretion. It is suggested that saliva sampling, instead of plasma sampling, to be used in bioavailability and bioequivalence studies for drugs that fall into classes I, II or III.
Idkaidek N, Najib N., " In Silico vs. In vivo Human Intestinal Permeability " , "Drug Res (Stuttg). 2014 Feb",Vol.,No., , , 02/01/2014
Idkaidek N, Arafat T, " Saliva vs. Plasma Bioequivalence of Metformin in Humans: Validation of Class II Drugs of the Salivary Excretion Classification System. " , "Drug Res (Stuttg). 2014 Jan",Vol.,No., , , 01/01/2014
Idkaidek N, Arafat T, " Saliva vs. Plasma Bioequivalence of Paracetamol in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System " , "Drug Res (Stuttg). 2014 Jan",Vol.,No., , , 01/01/2014
Jilani JA, Idkaidek , " Synthesis, In Vitro and In Vivo Evaluation of the N-ethoxycarbonylmorpholine Ester of Diclofenac as a Prodrug. " , "Pharmaceuticals (Basel). 2014 Apr 14;7(4):453-63",Vol.,No., , , 04/01/2014
Al-Ghazawi A, Idkaid, " Bioequivalence of two pregabalin 300 mg capsules (Neurexal and Lyrica®) in healthy human volunteers. " , "Drug Res (Stuttg). 2014 Jul;64(7):358-62.",Vol.,No., , , 07/01/2014
Nasir Idkaidek • Taw, " Saliva Versus Plasma Bioequivalence of Rusovastatin in Humans: " , "Drugs R D",Vol.,No., Springer, , 02/11/2015
Bioequivalence of rusovastatin in healthy
human volunteers was done using saliva and plasma
matrices in order to investigate the robustness of using
saliva instead of plasma as a surrogate for bioequivalence
of class III drugs according to the salivary excretion classification
system (SECS). Saliva and plasma samples were
collected for 72 h after oral administration of rusovastatin
40 mg to 12 healthy humans. Saliva and plasma pharmacokinetic
parameters were calculated by non-compartmental
analysis. Analysis of variance, 90 % confidence
intervals, and intra-subject and inter-subject variability
values of pharmacokinetic parameters were calculated
using Kinetica program V5. Human effective intestinal
permeability was also calculated by SimCYP program
V13. Rusovastatin falls into class III (high permeability/
low fraction unbound to plasma proteins) and hence was
subjected to salivary excretion. A correlation coefficient of
0.99 between saliva and plasma concentrations, and a saliva/
plasma concentration ratio of 0.175 were observed. The
90 % confidence limits of area under the curve (AUClast)
and maximum concentration (Cmax) showed similar trends
in both saliva and plasma. On the other hand, inter- and
intra-subject variability values in saliva were higher than in
plasma, leading to the need for a slightly higher number of
subjects to be used in saliva studies. Non-invasive saliva
sampling instead of the invasive plasma sampling method
can be used as a surrogate for bioequivalence of SECS
class III drugs when an adequate sample size is used.
Relative bioavailability study of tolterodine in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioavailability and bioequivalence of class III drugs according to the salivary excretion cl