Antimalarials

Background Hydroxychloroquine (HCQ), a 4-aminoquinolone antimalarial, is regarded as the oral therapy of choice for cutaneous and systemic lupus erythematosus (SLE). It is also licensed for rheumatoid arthritis (RA). Studies of HCQ-treated patients with SLE or RA have demonstrated a positive correlation between whole-blood HCQ levels and clinical response. Such studies have involved measuring whole-blood concentrations at any given time point after HCQ ingestion assuming that steady-state concentrations would undergo limited fluctuation over a daily interval because HCQ has a long half-life. This approach might not sufficiently take into account the potential intra-patient variation in HCQ blood levels that can occur over a 24-hour period. Such variation, if significant, could affect the credibility of any concentration-response relationship provided from these previous studies. Objectives The objectives of this report are to: (a) investigate the intra-patient variation in HCQ whole-blood levels and (b) suggest an optimum time for sampling patients for future studies. Methods Six patients were recruited with cutaneous lupus erythematosus who had each been on HCQ 200 mg twice daily for at least six months, so that they were at steady-state. Each patient was fasted overnight and had standardized meals and dosing schedule. Whole blood was sampled at seven time points over 24 hours. Whole-blood HCQ levels were measured with high-performance liquid chromatography using gradient elution, fluorimetric detection and chloroquine as an internal standard. The assay had a mean inter- and intra-day coefficient of variation of 10% and 5% respectively and a limit of detection of 5ng/ml. Results HCQ levels appeared to follow a biphasic pattern over the sampling period. Maximum levels were noted a median of four hours (range 2–6) after ingestion. Median intra-patient variation between trough and peak levels, ‘Cmax’ ((peak – trough)/trough × 100%), was 27% (range 8–150%). Conclusions This study demonstrated that whole-blood HCQ levels vary 27% (median, range 8–150%) within an individual over a 12-hour period. Drug levels might differ between individuals because of multiple factors, including variable adherence to medication. Measuring HCQ levels for assessment of drug adherence could be valuable in the ‘real-world’ clinical setting. This could be assessed by taking a blood sample at any time following HCQ ingestion. If patients were found to have very low or undetectable levels of HCQ, non-adherence to HCQ should be suspected.

show abstract

“…Bioavailability studies have shown that steady-state levels are reached after six months of therapy. 16–18…”

Section: Introductionmentioning

confidence: 99%

Steady-state pharmacokinetics of hydroxychloroquine in patients with cutaneous lupus erythematosus

Al-Rawi

Meggitt

Williams

et al. 2017

Lupus

View full text Add to dashboard Cite

show abstract

“…Cilt ile ilgili en sık görülen advers etkiler deri döküntüsü, kaşıntı ve saç dökülmesidir. Yapılan çalışmalarda daha nadir görülen morbiliform döküntüler, eritroderma, eksfoliyatif dermatit, ürtiker, ekzematöz erüpsiyonlar, ışığa duyarlılık ve eritema annulare centrifugum gibi kütanöz belirtiler de olduğu kaydedilmiştir (51,52).…”

Section: Güvenlilik Profiliunclassified

Klorokin/Hidroksiklorokin: COVID-19 tedavisi ile gündeme gelen eski bir ilaca farmakolojik bakış

Oğuz

Hodzic

Hatiboğlu

et al. 2020

Anadolu Kliniği Tıp Bilimleri Dergisi

View full text Add to dashboard Cite

Son yıllarda ilaç yeniden konumlandırma çalışmalarının hız kazanması ile özellikle zararsız olduğu kanıtlanmış, farmakokinetik ve optimal dozu iyi bilinen ilaçlar farklı endikasyonlarda kullanılmak üzere yeniden araştırmalara tabi tutulmaktadır. Günümüzde pandemiye neden olan SARS-CoV-2'ye karşı özellikle klinik olarak etkinliği kanıtlanmış tedavi ya da aşı henüz bulunmamıştır. COVID-19 hastalığının tedavisinde klorokin ve hidroksiklorokinin tedavi potansiyeli büyük ölçüde dikkat çekmiştir. Bu derlemede COVID-19'un tedavisi ile yeniden gündeme gelen eski bir ilaç olan klorokin/hidroksiklorokinin farmakokinetik, farmakodinamik özellikleri, özel popülasyonlardaki kullanımı ve güvenliği ile ilgili mevcut veriler incelenmiş ve literatürdeki güncel araştırmalar doğrultusunda SARS-CoV-2 enfeksiyonundaki etkinlik ve güvenliğine ilişkin veriler sunulmaktadır. Klorokin/Hidroksiklorokinin COVID-19 hastalığının tedavi algoritmalarında ilk sırada yer alması ile birlikte daha fazla randomize kontrollü klinik çalışmanın da gerekli olduğu görülmektedir.

show abstract

“…Se administran por vía oral, en dosis de 250 mg diarios (3,5 mg/kg) la cloroquina, y de 400 mg diarios (6,5 mg/ kg), la hidroxicloroquina [21][22][23] . La quinacrina es una 9-aminocridina con una farmacocinética muy similar a la de las dos anteriores; difiere en su estructura por un núcleo de acridina que contiene un anillo extra de benceno.…”

Section: Antipalúdicosunclassified

“…Sin embargo, es eficaz como monoterapia y en combinación con otros antipalúdicos en casos resistentes, pues potencia la acción de la cloroquina y la hidroxicloroquina. Además, al parecer, carece de toxicidad retiniana, por lo que se utiliza cuando hay alteraciones oculares previas que contraindican el uso de las cloroquinas 23,24 .…”

Section: Antipalúdicosunclassified

“…También pueden originar efectos secundarios gastrointestinales (náuseas, vómito y diarrea), cutáneos (pigmentación grisazulada, blanqueamiento de la raíz del pelo y bandas transversales en las uñas), neuromusculares y, menos frecuentes, cardiacos y hematológicos. Están contraindicados cuando existe retinopatía previa o hipersensibilidad conocida, y en pacientes que reciban tratamiento inmunosupresor de la médula ósea 22,23 .…”

Section: Antipalúdicosunclassified

See 1 more Smart Citation