Drugs in Semen

Clinical Biochemistry Unit, Istituto Superiore di Sanità, Rome, Italy.
Clinical Pharmacokinetics (Impact Factor: 5.05). 06/1994; 26(5):356-73. DOI: 10.2165/00003088-199426050-00004
Source: PubMed

ABSTRACT Over the past 50 years, a decline in the quality of semen has been observed, possibly resulting in a reduction in male fertility. Among the factors affecting semen quality, exposure to drugs is of particular importance. It is known that drugs can be transported to the seminal plasma, which is made up of secretions from the various accessory genital glands. There is evidence that many drugs enter the male genitourinary tract by an ion-trapping process. Lipid solubility and the degree of ionisation of the drug, which depend on the pH of plasma and seminal fluid, are important factors in this process. To date, few studies have been conducted on this topic. Pharmacokinetic evaluation of the fluids of the male accessory gland have been performed in the case of chloroquine and caffeine only, while the effects of mesalazine (5-aminosalicylic acid), sulfasalazine, salicylate, propranolol, diltiazem, flunarizine, verapamil, caffeine and nicotine on sperm physiology and morphology have been examined. Although data from the literature are scarce and incomplete, it is evident that many drugs can be excreted into semen. These drugs may interfere with the most common semen characteristics, potentially resulting in a male-mediated teratogenic effect, or local and systemic responses in female recipients. Therefore, it may be advisable to include, in the processes of drug development, pharmacokinetic evaluation of a drug in the semen and analysis of standard microscopic parameters of the semen. This is particularly important for drugs known to concentrate in the semen.

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    • "men are to ensure that the fetus is not exposed to the investigational medical product through seminal transfer and subsequent vaginal absorption. " In addition, the literature surrounding seminal excretion and vaginal absorption of drugs primarily addresses small molecules and does not cover the risk of biopharmaceuticals present in seminal fluid [1] [2]. The lack of data on seminal transfer and vaginal absorption of biopharmaceuticals represent a significant data gap given the high proportion of drugs that fall into this category. "
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    ABSTRACT: Studies were conducted in New Zealand White rabbits to assess the seminal transfer, vaginal absorption, and placental transfer of a therapeutic monoclonal antibody (T-IgG4). T-IgG4 was administered by intravenous injection (IV) in males and by IV and intravaginal routes in females. Low levels of T-IgG4 were excreted into seminal plasma (100- to 370-fold lower than serum concentrations) and absorbed following vaginal dosing (3 orders of magnitude lower than IV administration). On gestation day 29 (GD29), fetal serum T-IgG4 levels were 1.5-fold greater than maternal levels following IV dosing. The fetal T-IgG4 exposure ratio for seminal transfer vs. direct maternal IV dosing was estimated to be 1.3*10−8. Applying human serum T-IgG4 exposure data to the model, the estimated human T-IgG4 serum concentration from seminal transfer was 3.07*10−7 μg/mL, an exposure level at least 1000-fold lower than the T-IgG4-ligand dissociation constant (Kd) and at least 7 orders of magnitude lower than the in vivo concentration producing 20% inhibition of the target (EC20). These data indicate that excretion of a T-IgG4 into semen would not result in a biologically meaningful exposure risk to the conceptus of an untreated partner.
    Reproductive Toxicology 09/2014; 48. DOI:10.1016/j.reprotox.2014.07.024 · 3.23 Impact Factor
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    • "for ≥21 vs 4–7 ejaculations per month), which was confined to nonadvanced prostate cancer, while no association was observed for advanced prostate cancer.45 Although there is biological plausibility for an inverse association between ejaculation frequency and prostate cancer risk, ie, elimination of chemical carcinogens and toxins from the prostate or alteration of the composition of prostatic fluid through sexual activity,46 additional prospective information is required before firm conclusions can be drawn. "
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    ABSTRACT: At present, only three risk factors for prostate cancer have been firmly established; these are all nonmodifiable: age, race, and a positive family history of prostate cancer. However, numerous modifiable factors have also been implicated in the development of prostate cancer. In the current review, we summarize the epidemiologic data for age, location, and selected behavioral factors in relation to the onset of prostate cancer. Although the available data are not entirely consistent, possible preventative behavioral factors include increased physical activity, intakes of tomatoes, cruciferous vegetables, and soy. Factors that may enhance prostate cancer risk include frequent consumption of dairy products and, possibly, meat. By comparison, alcohol probably exerts no important influence on prostate cancer development. Similarly, dietary supplements are unlikely to protect against the onset of prostate cancer in healthy men. Several factors, such as smoking and obesity, show a weak association with prostate cancer incidence but a positive relation with prostate cancer mortality. Other factors, such as fish intake, also appear to be unassociated with incident prostate cancer but show an inverse relation with fatal prostate cancer. Such heterogeneity in the relationship between behavioral factors and nonadvanced, advanced, or fatal prostate cancers helps shed light on the carcinogenetic process because it discerns the impact of exposure on early and late stages of prostate cancer development. Inconsistent associations between behavioral factors and prostate cancer risk seen in previous studies may in part be due to uncontrolled detection bias because of current widespread use of prostate-specific antigen testing for prostate cancer, and the possibility that certain behavioral factors are systematically related to the likelihood of undergoing screening examinations. In addition, several genes may modify the study results, but data concerning specific gene-environment interactions are currently sparse. Despite large improvements in our understanding of prostate cancer risk factors in the past two decades, present knowledge does not allow definitive recommendations for specific preventative behavioral interventions.
    Clinical Epidemiology 01/2012; 4(1):1-11. DOI:10.2147/CLEP.S16747
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    • "Blood plasma pH 7.2 exceeds the pK a of most PIs and conditions favour increased membrane permeability; PIs are basic molecules that should accumulate in acidic compartments such as prostatic fluid (pH 6.6) by ion trapping (Kashuba et al 1999). Observed drug concentrations in prostatic fluid are, however, lower than predicted (Pichini et al 1994). The pharmacokinetic factors that favour PI penetration may be overridden because PIs bind to plasma proteins such as albumin and a 1 -acid glyco- protein. "
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    ABSTRACT: Antiretroviral therapy has reduced the morbidity and mortality associated with HIV-1/AIDS in developed countries. Viral replication in blood plasma is suppressed by antiretroviral drugs, whereas virus in the male genital tract is genetically and phenotypically unique and may not be suppressed. This viral compartmentalization affects antiretroviral drug penetration of the male genital tract and capacity for antiretroviral therapy to reduce sexual transmission. The problem of having two distinct viral populations within any given individual is compounded by the fact that antiretroviral drugs penetrate semen to varying degrees. Incomplete suppression of genital tract virus may yield drug-resistant virus and increase the risk of sexual transmission. This review critically appraises current studies of antiretroviral drug quantification in semen and suggests recommendations to address observed limitations.
    Journal of Pharmacy and Pharmacology 12/2007; 59(11):1451-62. DOI:10.1211/jpp.59.11.0001 · 2.26 Impact Factor
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