Effect of Microgravity on the Pharmacokinetics of Ibuprofen in Humans

Idkaidek, Nasir; Arafat, Tawfiq

doi:10.1177/0091270010388652

Cited by 21 publications

(12 citation statements)

References 8 publications

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“…The relative bioavailability of etacizine was increased during HDT BR (Polyakov et al, 2021). Finally, no relevant differences in PK parameters were observed for orally administered ibuprofen after 1‐day of HDT BR (angle not‐specified) (Idkaidek & Arafat, 2011), whereas 30% increased exposure to promethazine was found after 2‐days of 6° HDT BR, especially when the drug was administered per os (Gandia et al, 2006).…”

Section: Drug Pk Studies In Space and In Surrogate Models Of Microgra...mentioning

confidence: 99%

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Russo

Bandiera

Monici

et al. 2022

British J Pharmacology

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As human spaceflight progresses with extended mission durations, the demand for effective and safe drugs will necessarily increase. To date, the accepted medications used during missions (for space motion sickness, sleep disturbances, allergies, pain, and sinus congestion) are administered under the assumption that they act as safely and efficaciously as on Earth. However, physiological changes have been documented in human subjects in spaceflight involving fluid shifts, muscle and bone loss, immune system dysregulation, and adjustments in the gastrointestinal tract and metabolism. These alterations may change the pharmacokinetics (PK) and pharmacodynamics of commonly used medications. Frustratingly, the information gained from bed rest studies and from in‐flight observations is incomplete and also demonstrates a high variability in drug PK. Therefore, the objectives of this review are to report (i) the impact of the space environmental stressors on human physiology in relation to PK; (ii) the state‐of‐the‐art on experimental data in space and/or in ground‐based models; (iii) the validation of ground‐based models for PK studies; and (iv) the identification of research gaps.

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Section: Drug Pk Studies In Space and In Surrogate Models Of Microgra...mentioning

confidence: 99%

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Russo

Bandiera

Monici

et al. 2022

British J Pharmacology

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“…Regulation occurs at the level of protein digestion and amino acid absorption (128), the insulin-stimulated (postprandial) increase in muscle tissue perfusion (119,178), the uptake of amino acids in skeletal muscle (54), intramyofibrillar anabolic signaling (34,60), and the initiation or inhibition of muscle protein synthesis or breakdown rate (159). Muscle disuse, and particularly (head-down tilted) bed rest, may also modulate the digestion and absorption of ingested foods (56,76,80). Additionally, physical inactivity could lead to impairments in insulin-mediated tissue perfusion, would impair amino acid delivery to the muscle, and attenuate the postprandial rise in muscle protein synthesis rates (119).…”

Section: Leg Immobilizationmentioning

confidence: 99%

Interventional strategies to combat muscle disuse atrophy in humans: focus on neuromuscular electrical stimulation and dietary protein

Dirks

Wall

Loon

2018

Journal of Applied Physiology

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Numerous situations, such as the recovery from illness or rehabilitation after injury, necessitate a period of muscle disuse in otherwise healthy individuals. Even a few days of immobilization or bed rest can lead to substantial loss of skeletal muscle tissue and compromise metabolic health. The decline in muscle mass is attributed largely to a decline in postabsorptive and postprandial muscle protein synthesis rates. Reintroduction of some level of muscle contraction by the application of neuromuscular electrical stimulation (NMES) can augment both postabsorptive and postprandial muscle protein synthesis rates and, as such, prevent or attenuate muscle loss during short-term disuse in various clinical populations. Whereas maintenance of habitual dietary protein consumption is a prerequisite for muscle mass maintenance, supplementing dietary protein above habitual intake levels does not prevent muscle loss during disuse in otherwise healthy humans. Combining the anabolic properties of physical activity (or surrogates) with appropriate nutritional support likely further increases the capacity to preserve skeletal muscle mass during a period of disuse. Therefore, effective interventional strategies to prevent or alleviate muscle disuse atrophy should include both exercise (mimetics) and appropriate nutritional support.

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“…Salivary excretion investigated in this study was for sitagliptin, cinacalcet, metformin, montelukast, tolterodine, hydrochlorothiazide (HCT), lornoxicam, azithromycin, diacerhein, rosuvastatin, cloxacillin, losartan and tamsulosin. Paracetamol, phenytoin, carbamazepine, fluconazole, norfloxacin, erythromycin and ibuprofen salivary excretion has been investigated previously. ,− …”

Section: Introductionmentioning

confidence: 99%

Saliva versus Plasma Pharmacokinetics: Theory and Application of a Salivary Excretion Classification System

Idkaidek

Arafat

2012

Mol. Pharmaceutics

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The aims of this work were to study pharmacokinetics of randomly selected drugs in plasma and saliva samples in healthy human volunteers, and to introduce a Salivary Excretion Classification System. 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 noncompartmental analysis using the Kinetica program. Effective intestinal permeability (P eff) values were estimated by the Nelder–Mead algorithm of the Parameter Estimation module using the SimCYP program. P eff values were optimized to predict the actual average plasma profile of each drug. All other physicochemical factors were kept constant during the minimization processes. 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 P eff ranged 0.16–44.16 × 10–4 cm/s, 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 Excretion Classification System (SECS) 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 SECS. 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. The proposed Salivary Excretion Classification System (SECS) can be used as a guide for drug salivary excretion. Future work is planned to test these initial findings, and demonstrate SECS robustness across a range of carefully selected (based on physicochemical properties) drugs that fall into classes I, II or III.

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Effect of Microgravity on the Pharmacokinetics of Ibuprofen in Humans

Cited by 21 publications

References 8 publications

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Interventional strategies to combat muscle disuse atrophy in humans: focus on neuromuscular electrical stimulation and dietary protein

Saliva versus Plasma Pharmacokinetics: Theory and Application of a Salivary Excretion Classification System

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