Pharmacokinetics and Pharmacodynamics, Article Review Example

Pharmacokinetics and Pharmacodynamics of Minocycline in Bronchopulmonary Infections

Introduction

Pharmacokinetics refers to the time taken for a particular drug to be absorbed and distributed into the whole body for metabolism to occur, followed by excretion. Pharmacokinetics principles apply in clinics when delivering drugs to patients, and it is always  done in an effective and safe way. Before a drug is accepted for clinical benefit, all four stages of pharmacokinetics are critically assessed. On the other hand, pharmacodynamics deals with the study of the molecular structure of drugs. Besides, the physiological and biochemical actions and effects are critically assessed. Besides, minocycline is a tetracycline that aids in fighting bacteria within the body and treats various infections related to bronchopulmonary. Therefore, the discussion focuses on reviewing articles related to minocycline treatment of bronchopulmonary infections.

Summary

The unbound drug area is associated with the effect of 24-hour bacteriostat, which is about 16.4 (Alfouzan et al., 2017, p.715). The drop in bacteria log is almost the log of -1, indicating a bacterial load drop of about 23.3. Within 48 hours, no strain dropped to -2 drop. Some changes occur among two of the three strains. Many strains are likely to be exposed to minocycline when 400mg are used daily within 24 hours. When treating Acinetobacter baumannii, there is a need to use more than 400mg a day or combination therapy with minocycline (Alfouzan et al., 2017, p.715). When minocycline is used against Staphylococcus aureus, a free drug AUC/MIC dominates confirming the existing regimen of 100mg for a duration of 12 hours (Bowker et al., 2008, p. 4371). The dose helps in achieving the pharmacodynamic target. Besides, during bronchopulmonary infection therapy, the average concentration of minocycline in sputum dose became 200mg for a day. It was about 0.83 ?g/ml, which amounted to almost 60% of the drug’s serum level Brogan et al. (1977, p. 250). Introduction of minocycline and tetracycline drugs during bronchopulmonary infection treatment results in the appearance of both drugs in the lymph within 30 minutes after infusion (Cohen et al., 1987, p.55). Peak concentration occurred 5 minutes post fusion of both drugs.

Some drugs may be preferred to treat pulmonary infections, unlike others. Despite minocycline being preferred to treat certain infections, there are times when doxycycline is highly preferred (Cunha et al., p. 2018, p.18). However, both drugs treat pulmonary infections. Echeverria et al. (2017, p.48) realized a difference in oral bioavailability among adult horses, and there was a detection of minocycline in BAL and PELF cells after 3 hours of drug administration. During feeding, oral bioavailability is reduced. Besides, when comparing the pharmacokinetics of minocycline among adult horses and foals, the results indicate no significant difference among them (Giguère et al., 2017, p.335). There is a high bioavailability in foals, unlike in adult horses. During research to profile injection of minocycline, it came out that the PK-PD profile among patients is greater than 1mg/l (Lodise et al., 2021, p.20). Besides, the two covariates retained were albumin and the body’s surface area. Human beings seem to have a half-life that is almost similar to doxycycline, that it is longer compared to that of tetracycline. Research indicates complete absorption via oral administration (Macdonald et al., 1973, p. 857). Besides, tetracyclines have fewer lipophilic properties when compared to minocycline. In addition, when using minocycline and doxycycline to treat respiratory disease, there were high levels of doxycycline in blood while sputum had high levels of minocycline (Maesen et al., 1989, p. 123). It is because doxycycline has extremely higher penetration. Besides, there was a difference in minocycline due to the two antibodies used.

Moreover, when assessing minocycline tissue distribution of pharmacokinetics, it is clear that there are no adverse effects experienced (Nagata et al., 2010, p.1064). The concentration of plasma, in that case, became 0.12 ?g/mL every 12 hours. The experiment proved no detection of minocycline in brain tissues. Assessment of minocycline penetration proved equal penetration of minocycline in erythrocytes and plasma, though other tissues had a high concentration (Naline et al., 1991, p.404). An insignificant difference existed between drug concentration in plasma and mucus. A Monte Carlo simulation may be used in evaluating minocycline and tigecycline efficacy to treat pneumonia. Ni et al. (2018, p.507) found out that the susceptibility rate for minocycline is 41.5% while for tigecycline is 79.9%. Noel et al. (2021, p.1843) did research by combining rifampicin and the pharmacodynamics of minocycline. They realized that when they added more rifampicin, there was an increased resistance reduction in a load of staphylococcus. However, there was no resistance by using minocycline. Assessment of carbapenem-resistance on gram-negative bacilli by the research done by Pogue et al. (2014, p.388) proved that the addition of minocycline could help treat carbapenem resistance. The earliest experience of the study had a positivity rate of 67% for those patients who had an infection. Ruth et al. (2019, p.1952) assessed the treatment of mycobacterium avium complex using minocycline. They realized that minocycline reduced the burden of the bacteria after using a dosage of 400mg daily.

Additionally, the second generational tetracyclines are minocycline and doxycycline. Saivin and Houin (988, p.355) reviewed the basic pharmacokinetics of the two molecules. The study results proved a high incompatibility with the observation made between minocycline and doxycycline. During the assessment of penetration and safety of pharmacokinetics, Schnabel et al. (2012, p.453) realized that minocycline had a high potential for both anti-inflammatory and anti-microbial effects. Tarazi et al. (2019, p. 18) assessed how minocycline acts on Acetobacter baumannii. The results of the study managed to achieve the existing FDA-approved dosage. Therefore, there was a need to administer 100 to 200mg doses twice daily. Tsakris et al. (2019, p.297) assessed the breakpoint susceptibility of Acinetobacter baumannii and found out that the existing breakpoint is 8-fold that is elevated according to the regime dosage that is approved. Finally, Tynan et al. (2016, p.257) assessed pharmacokinetics among domestic cats while narrowing down to minocycline. The results showed that the two cats became transiently tachypneic and lethargic when infused with the drug. Therefore, protein-plasma binding was 60%, while oral bioavailability was 62%.

Watanabe et al. (2001, p.7) assessed how minocycline hydrochloride penetrates sputum and lung tissues. It was realized that there was an effect on the ratio of serum and tissue. The serum concentration of minocycline hydrochloride was high compared to that of oral administration. Wei et al. (2015, p. 850) realized that minocycline is more effective when treating Stenotrophomonas maltophilia when compared to other drugs like levofloxacin, moxifloxacin, and tigecycline. In addition, SXT and minocycline are effective in treating S. maltophilia (Wei et al., 2016, p.32). Wood et al. (1975, p.330) found that 90 strains of Streptococcus pneumonia and Haemophilus species were inhibited by 2ug/ml of minocycline. However, the resistance of tetracycline remained above attainable levels of blood. Zhou et al. (2017, p.16) realized that minocycline effectively treated A. baumannii.

Critique

Strengths

These sources had various strengths. Bowker et al. (2008, p. 4371) the longer dosing simulation benefited the study due to longer exposure and assessing resistance emergency, leading to reliable results. A high concentration of tetracycline in lymph during bronchopulmonary infection treatment is important and an essential strength as it helps during tetracycline selection (Cohen et al., 1987, p.55). The effectiveness of doxycycline makes it highly preferred for treating systemic infections, which is an important strength (Cunha et al., p. 2018, p.18). The research by Echeverria et al. (2017, p.51) had a greater contribution when they realized that there was no difference in drug action between sedated and unsedated animals. In addition, the study by Lodise et al. (2021, p.20) was helpful since it found out that the breakpoint for FDA susceptibility was less than 4mg/L. One of the strengths in the study, Maesen et al. (1989, p.123), is that the two drugs had identical clinical results implying that a person can either use minocycline or tetracycline. One of the strengths that supported the study by Nagata et al. (2010, p.1064) is that many studies exit supporting the activity of minocycline against the strains of S. aureus in vitro pharmacokinetic model. One of the strengths that facilitated the achievement of better results by Ruth et al. (2019, p.1952) is that they could easily identify repurposed or new antibiotics. Also, they could integrate promising compounds into existing regimes. The study by Schnabel et al. (2012, p.453) had several strengths, including supporting oral administration of minocycline which most of the research did not achieve.

Weaknesses

Moreover, some articles have weaknesses. Despite the efforts by Bowker et al. (2008, p. 4371), there were some weaknesses during the study. First, the researchers ended up using a longer rifampin half-life, unlike it occurs in human beings due to some technical limitations. Second, treatment of chronic bronchitis exacerbations using tetracycline is questionable, which creates a weakness since tetracycline is quite inactive during vitro action compared to minocycline (Cohen et al., 1987, p.55). Third, there is high unfamiliarity of the spectrum of doxycycline and minocycline; hence, the two pose a limitation in their usage since it is not easy to interpret susceptibility results (Cunha et al., p. 2018, p.18). Besides, the study done by Lodise et al. (2021, p.20) has its limitations because it is not easy to put them into practice unless a clinical confirmation is done to prove the same; therefore, just like all PK-PD profiling, unless they are confirmed clinically, they won’t be applied. Also, the other weakness is that there exists limited published information on PK profile, therefore it is impossible to refer or to make references (Lodise et al., 2021, p.20). In addition, the study by Maesen et al. (1989, p.123) had some weaknesses since it was not easy to eradicate Haemophilus influenza posing a challenge since it meant that either doxycycline or minocycline was not effective. When assessing minocycline concentration, the study by Naline et al. (1991, p.404) had some weaknesses. When one assays minocycline in sputum collection, the results obtained are different from existing literature. Instead of indicating a low concentration of minocycline in the lungs, it indicates a high concentration.

Additionally, the study by Ni et al. (2018, p.507) has some limitations. The proposed dose of tigecycline of 100mg every 12 hours is not normally effective as the patient may still feel sick hence requiring doubling of the dose for one to feel better. In addition, the research by Noel et al. (2021, p.1843) had some weaknesses since limited use of rifampicin posed a challenge since it resulted in resistance of the drug by staphylococcal load causing its infectiveness. One of the weaknesses of the study done by Nagata et al. (2010, p.1064) is that various clinical limitations arise from the troublesome and resistance of carbapenem since it causes an increase in infections. Besides, it is not clear whether the high dose of 200mg after every 12 hours is closely associated with clinical outcomes. One of the challenges of the study done by Ruth et al. (2019, p.1952) is that it is not clinically proven effective; therefore, it does not apply to patients. Besides, synergy and MIC data is likely to underestimate the tetracycline effect when treating intracellular pathogens. The other challenge is that the assays are static, and they do not involve continuous addition of drugs, other than the one added at the beginning, making it an impossible model for humans (Ruth et al., 2019, p.1952). Furthermore, there was no information on elderly subjects concerning minocycline when assessing age differences, leading to more approximations (Saivin & Houin, 1988, p.355).

One of the weaknesses presented by Schnabel et al. (2012, p.453) is that they could not determine an effective dose that could help treat ocular infections; hence, there is a need for further research. One of the limitations affecting Tsakris et al. (2019, p.297) research is that minocycline studies are scarce, making it impossible to compare obtained results and make reference. The study by Tynan et al. (2016, p.257) had various limitations. First, only domestic cats were used for the study; therefore, there might be different results if wild cats were introduced. Also, if cats of different ages were used, different results might have been obtained. Besides, the sample size was too small, that is, six cats, rendering the results unreliable (Tynan et al., 2016, p.257).

Opinion

These authors have contributed a lot to this field. Alfouzan et al. (2017, p.715) helped understand the right quantity of drug needed per day when treating Acinetobacter baumannii, which was 400mg daily or combining therapy with minocycline; hence, I support the study. Bowker et al. (2008, p. 4371) helped understand the clinical breakpoints of Staphylococcus aureus and tetracycline, and therefore, I support the study. Besides, the study by Brogan et al. (1977, p. 250) contributed to understanding that minocycline intrabronchial concentration does not depend on the pulmonary vascular bed’s inflammatory response during therapy. Also, there is an active section of minocycline into the bronchial lumen by bronchial epithelial glands and cells. Therefore, I agree with this support by Brogan et al. (1977, p. 250). Tetracycline has a high penetration capability into extra-blood vascular is highly recommended for pulmonary infections treatment (Cohen et al., 1987, p.55). Doxycycline and minocycline pose some differences and similarities when using them for treatment, though these drugs should be used since they are effective in different ways (Cunha et al., p. 2018, p.18). I recommend the study done by Echeverria et al. (2017, p.48) because it came out clearly that tetracyclines have better anti-microbial activity against a majority of Streptococcus species. In addition, I recommend the article by Giguère et al. (2017, p.335) because, through it, it was easier to realize that there is no difference in the pharmacokinetics of minocycline among adult horses and foals, implying that the objective of the study was well achieved.

Furthermore, I recommend the study done by Lodise et al. (2021, p.20) since they could profile minocycline among patients who had A. baumannii. It is not possible to find consistency between experimental animals and human beings in some cases. However, the study by Macdonald et al. (1973, p. 857) indicates consistency. I support this research. Doxycycline and minocycline help treat respiratory infections, and I recommend this research by Maesen et al. (1989, p.123) because an insignificant difference exists between the two drugs. One of the study’s contributions by Nagata et al. (2010, p.1064) is that minocycline is useful in treating various infections within the body, including the CNS. I support it. I do not support the study by Naline et al. (1991, p.404) since it indicates the opposite of what the literature states. For instance, instead of having a low concentration of minocycline in the lungs, it shows a high concentration. I support the research done by Ni et al. (2018, p.507) when using a Monte Carlo simulation in evaluating minocycline and tigecycline efficacy to treat pneumonia since the treatment becomes more effective when the dose is doubled to 200mg every 12 hours. I support the study by Noel et al. (2021, p.1843), which focused on combining rifampicin and pharmacodynamics of minocycline, and later on realized that there was a need to increase rifampicin to reduce the resistance of S. aureus. I support the study done by Nagata et al. (2010, p.1064) because they could control infection among patients by adding minocycline to help treat carbapenem resistance.

Moreover, I support the research done by Ruth et al. (2019, p.1952) since they were able to use minocycline to reduce the burden of the bacteria after using a dosage of 400mg. I support the study by Saivin and Houin (988, p.355) since they displayed a high drug interaction leading to treatment of the corresponding challenges. Generally, I support the study by Schnabel et al. (2012, p.453); they managed to determine the part of the body that had the highest concentration and drug administration. Also, the research supports the use of oral drug administration. Therefore, I support the study by Tarazi et al. (2019, p. 18) because they could determine the right dose as expected by the FDA. I recommend the study done by Tsakris et al. (2019, p.297) because it offers an alternative way of treating baumannii strain infections that happen to retain minocycline susceptibility. I support Tynan et al. (2016, p.257) study because it introduced oral minocycline, which is highly reasonable, and cats can tolerate it. I support the study done by Watanabe et al. (2001, p.7) because it proved that minocycline hydrochloride is effective when treating infections in the respiratory tract. I recommend the study done by Wei et al. (2015, p. 850) since it proved that minocycline is highly effective when treating Stenotrophomonas maltophilia. I support the study by Wei et al. (2016, p.32) due to the effectiveness of proposed drugs like SXT and minocycline. I support the study by Wood et al. (1975, p.330) because they were to effectively use minocycline to control Streptococcus pneumoniae and Haemophilus species. I support the study done by Zhou et al. (2017, p.16) because they managed to find out how to control A. Baumannii using minocycline.

Conclusion

Decisively, pharmacokinetics is critical in the clinical setting to understand the functionality of different drugs. Such helps in ensuring the safety of patients to prevent them from harm and understand the time when they should recover, and if not, change the medication. On the other hand, pharmacodynamics helps in understanding the structures and behaviour of drugs hence useful when assessing all biochemical actions of drugs. Generally, after reviewing these articles, it is clear that some researches were perfect due to the availability of certain strengths that supported them. In contrast, others had some limitations hindering their success. Besides, these sources had a great contribution and hence recommended for use.

References

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